发育阶段相关基因的结构特征，基因组特征和起源进化
|
摘要
哺乳动物基因的表达模式同其分子结构特征之间的关联以及这些结构特征的进化规律是生物学中基本问题,但这些问题仍有待深入研究。发育进程被认为对于探索进化机制至关重要,而哺乳动物的干细胞分化系统,包括干细胞,祖细胞和其分化产物,也提供了一个描述哺乳动物发育进程的理想模型。因此,本文以小鼠干细胞分化模型中与发育阶段相关的基因表达模式为基础,试图建立哺乳动物基因的表达模式与其分子结构特征之间的关联。
在不同的细胞类型中,我们建立了基因表达量同密码子使用偏好的关联。我们发现,处于不同发育阶段的细胞,其优化密码子可能会有所不同。在小鼠基因中,GC结尾密码子的使用在整体上占据优势;但我们却在相当多种类的处于早期发育阶段的干细胞和祖细胞中,发现优化密码子以AT结尾。我们还发现,在不同发育阶段中富集表达(发育阶段关键基因)或特异性表达(发育阶段特异性基因)的基因,也可能具有不同的密码子使用模式。而且,对于同一个发育阶段,特异性表达的基因与富集表达的基因相比,往往使用更多的以GC结尾的同义密码子。进一步的分析暗示,上述与发育阶段相关的密码子偏好模式,特别是以AT结尾的优化密码子在很大程度上与翻译选择模型的预言相一致。
在哺乳动物中,基因的密码子偏好(GC3)与基因所在基因组区域的GC含量(GCg)密切相关。我们的结果表明,小鼠基因所在基因组区域的GCg也同其发育阶段相关。进一步,我们还分析了小鼠发育阶段相关基因在基因组上分布和排列的规律。我们发现,发育阶段相关基因在各个染色体上的分布并不均匀,这可能意味着各个染色体对分化进程的贡献各异。我们还发现,很多与发育阶段密切相关的基因在染色体上呈现成簇分布的状态,并且,簇内基因与簇外基因相比,偏好于使用更多以GC结尾的同义密码子。
我们接下来通过比较基因组学的方法研究了发育阶段相关基因在起源和进化上的初步规律。首先,我们的结果表明,高表达基因的进化速率要低于中—低表达基因的进化速率,这暗示在人—小鼠以及大鼠—小鼠分歧后对高表达基因的负选择仍然有效。与之相反,对于那些在某个发育阶段中选择性表达的发育阶段关键基因或发育阶段特异性基因,其进化速率往往显著高于那些表达模式不随发育阶段变化的基因。较高的进化速率暗示这些基因在人—小鼠以及大鼠—小鼠分歧后可能受到了不同的功能性制约。其次,我们发现,热血动物的直系同源基因间具有比较相似的密码子偏好模式,这暗示了小鼠的密码子使用偏好在热血动物共同祖先出现时已基本固定。最后,我们还发现,高表达基因与中—低表达基因相比,以及表达模式不随发育阶段变化的基因同在某个发育阶段中选择性表达的发育阶段关键基因或发育阶段特异性基因相比,通常能够在果蝇基因组中找到更多的直系同源基因。我们的结果表明,小鼠基因的表达模式和分子特征均与其古老程度相关。
上述分析依赖于已发表的小鼠干细胞及其分化产物的高通量表达数据;而且,这些数据中仅包括来自外胚层和中胚层的前体细胞。我们接下来要探索,在内胚层的分化路径中,小鼠基因的密码子偏好,基因组GC含量,基因分布和基因年龄是否仍同与发育阶段相关的基因表达模式有关。我们在小鼠成体胰腺的体外培养体系中鉴定了一群具有增殖和多向分化能力的前体细胞,并发现这群细胞分布于胰岛中和导管周边。我们进一步分析了该群前体细胞和胰腺成熟内分泌细胞(胰岛)的基因表达谱,发现在胰腺前体细胞和胰岛细胞组成的分化模型中,基因分子特征,基因组特征和起源进化的相关规律也在相当的程度上与其所处的发育阶段有关,且基本规律与我们在外胚层和中胚层中观察到的相同或相近。
在本文中,我们应用干细胞分化模型,为研究哺乳动物分子进化中的一些关键问题提供了有价值的线索。例如,我们发现了哺乳动物密码子偏好使用的新规律,提出了支持自然选择作用于哺乳动物同义位点的新证据。此外,我们的研究结果对于理解哺乳动物基因的进化历程和哺乳动物基因组GC含量的潜在生物学意义都提供了新的途径。
这项研究将分子进化的理论分析引入干细胞领域,对于从结构特征的角度,在基因组尺度上理解干细胞的标志性分子和分化机理也具有一定的意义。我们的结果显示,干细胞和成熟细胞差异表达的基因在分子结构特征上存在差异;并且,在干细胞分化进程中经历结构变化的染色质片段,也可能与这些片段的GC含量有关。我们的这些结果,其深入意义还有待于进一步的研究和开掘。
The identification of the correlations between the molecular features of mammalian genes and their patterns of expression, as well as the exploration of the evolutionary processes of these molecular features are fundamental biological issues and remain subjects of controversy. Developmental processes are believed to be of critical importance to the investigation of evolutionary mechanisms. Moreover, stem cells, progenitor cells and their derivates, defined by their distinct differentiation potential, provide ideal models of the mammalian developmental hierarchy. Therefore, in this thesis, we tried to establish the correlations between the molecular features of mammalian genes and their patterns of expression, based on the developmental stage-related patterns of gene expression in models of mouse stem cell differentiation.
We established the correlations between the levels of gene expression and codon usage in different cell types. Our results showed that the optimal codons exhibited variation within the developmental hierarchy. Specifically, in certain mouse stem cells and progenitor cells in early developmental stages of ontogeny, the optimal codons were the AT-ending ones, while the mouse major codons are the GC-ending ones. We also found that genes that were enriched (developmental-pivotal genes, DPGs) or specifically expressed (developmental-specific genes, DSGs) at different developmental stages had different patterns of codon usage. Moreover, at the same developmental stage, DSGs generally used more GC-ending codons compared with DPGs. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons.
It has been indicated that codon usage (GC3) and local genomic GC content (GCg) are closely correlated in mammalian genome. Our results also showed that the variations of GCg were correlated with the developmental-stage related patterns of gene expression. We further investigated the distribution and organization of developmental stage-related genes in mouse chromosomes. We found that the distributions of genes corresponding to each developmental stage were not homogeneous among different chromosomes, suggesting the contributions of different chromosomes could be distinct at each developmental stage. We also observed that many developmental stage- related genes were organized as clusters in chromosomes. Moreover, genes within clusters generally used more GC-ending codons than genes out of the clusters.
By a comparative genomics approach, we further investigated the origin and the evolutionary processes of developmental stage-related genes. First, our data showed that the evolutionary rates of highly expressed genes were lower than that of mid-lowly expressed genes, indicating the influence of selective constraints on highly expressed genes was still detectable after the human-mouse and mouse-rat divergence. In contrast with these observations, DPGs and DSGs generally had higher evolutionary rates than non-developmental-pivotal genes (NDPGs). The higher rates might infer different functional constraints of these genes after the human-mouse and mouse–rat divergence. Second, we indicated that there were similar patterns of codon usage among orthologous genes of warm-blood vertebrates. These results suggested that the codon usage biases of mouse genes were formed in the common ancestor of warm-blood vertebrates. Third, we found highly expressed genes and NDPGs, compared with mid-lowly expressed genes and developmental-selectively expressed genes (DPGs and DSGs) respectively, could find more orthologous genes in genome of fruit fly. We also showed that both expression patterns and molecular features were correlated with the age of mouse genes.
The investigations above are dependent on the published high-throughput studies of stem cells and their derivates from ectoderm and mesoderm. We in turn to explore whether the codon usage, genomic GC content, gene distribution, and gene age are also correlated with the developmental stage- related patterns of gene expression in differentiation processes of endoderm. We defined a precursor cell population from adult mouse pancreas by selective culture. We found these precursor cells were located in the islets and around the pancreatic ducts. Based on the analyses of the expression profiling of both this pancreatic precursor cell population and mouse islets, our data showed that the molecular features, genomic characteristics and evolutionary processes are also correlated with developmental-stage related patterns of gene expression in endoderm, generally consistent with the observations in ectoderm and mesoderm.
Using the models of stem cell differentiation, the current study provides certain useful clues of evolutionary issues at the molecular level. For example, we showed new patterns of mammalian codon usage and new evidence of the presence of natural selection at mammalian synonymous sites. Moreover, our data also assist our understanding of the biological meaning of genomic GC content and the evolutionary processes of mammalian genes.
The current study has applied theoretical analyses of molecular evolution into stem cell research to gain a better understanding of stem cell differentiation at the genomic level. For example, we found that mammalian genes that specifically expressed at different developmental stages bear different molecular features. In addition, we also suggested that the genome segments that are involved in chromatin remodeling might correlate with their GC content. Further investigation will be needed to better understand the significance and implications of the findings presented here.
在不同的细胞类型中,我们建立了基因表达量同密码子使用偏好的关联。我们发现,处于不同发育阶段的细胞,其优化密码子可能会有所不同。在小鼠基因中,GC结尾密码子的使用在整体上占据优势;但我们却在相当多种类的处于早期发育阶段的干细胞和祖细胞中,发现优化密码子以AT结尾。我们还发现,在不同发育阶段中富集表达(发育阶段关键基因)或特异性表达(发育阶段特异性基因)的基因,也可能具有不同的密码子使用模式。而且,对于同一个发育阶段,特异性表达的基因与富集表达的基因相比,往往使用更多的以GC结尾的同义密码子。进一步的分析暗示,上述与发育阶段相关的密码子偏好模式,特别是以AT结尾的优化密码子在很大程度上与翻译选择模型的预言相一致。
在哺乳动物中,基因的密码子偏好(GC3)与基因所在基因组区域的GC含量(GCg)密切相关。我们的结果表明,小鼠基因所在基因组区域的GCg也同其发育阶段相关。进一步,我们还分析了小鼠发育阶段相关基因在基因组上分布和排列的规律。我们发现,发育阶段相关基因在各个染色体上的分布并不均匀,这可能意味着各个染色体对分化进程的贡献各异。我们还发现,很多与发育阶段密切相关的基因在染色体上呈现成簇分布的状态,并且,簇内基因与簇外基因相比,偏好于使用更多以GC结尾的同义密码子。
我们接下来通过比较基因组学的方法研究了发育阶段相关基因在起源和进化上的初步规律。首先,我们的结果表明,高表达基因的进化速率要低于中—低表达基因的进化速率,这暗示在人—小鼠以及大鼠—小鼠分歧后对高表达基因的负选择仍然有效。与之相反,对于那些在某个发育阶段中选择性表达的发育阶段关键基因或发育阶段特异性基因,其进化速率往往显著高于那些表达模式不随发育阶段变化的基因。较高的进化速率暗示这些基因在人—小鼠以及大鼠—小鼠分歧后可能受到了不同的功能性制约。其次,我们发现,热血动物的直系同源基因间具有比较相似的密码子偏好模式,这暗示了小鼠的密码子使用偏好在热血动物共同祖先出现时已基本固定。最后,我们还发现,高表达基因与中—低表达基因相比,以及表达模式不随发育阶段变化的基因同在某个发育阶段中选择性表达的发育阶段关键基因或发育阶段特异性基因相比,通常能够在果蝇基因组中找到更多的直系同源基因。我们的结果表明,小鼠基因的表达模式和分子特征均与其古老程度相关。
上述分析依赖于已发表的小鼠干细胞及其分化产物的高通量表达数据;而且,这些数据中仅包括来自外胚层和中胚层的前体细胞。我们接下来要探索,在内胚层的分化路径中,小鼠基因的密码子偏好,基因组GC含量,基因分布和基因年龄是否仍同与发育阶段相关的基因表达模式有关。我们在小鼠成体胰腺的体外培养体系中鉴定了一群具有增殖和多向分化能力的前体细胞,并发现这群细胞分布于胰岛中和导管周边。我们进一步分析了该群前体细胞和胰腺成熟内分泌细胞(胰岛)的基因表达谱,发现在胰腺前体细胞和胰岛细胞组成的分化模型中,基因分子特征,基因组特征和起源进化的相关规律也在相当的程度上与其所处的发育阶段有关,且基本规律与我们在外胚层和中胚层中观察到的相同或相近。
在本文中,我们应用干细胞分化模型,为研究哺乳动物分子进化中的一些关键问题提供了有价值的线索。例如,我们发现了哺乳动物密码子偏好使用的新规律,提出了支持自然选择作用于哺乳动物同义位点的新证据。此外,我们的研究结果对于理解哺乳动物基因的进化历程和哺乳动物基因组GC含量的潜在生物学意义都提供了新的途径。
这项研究将分子进化的理论分析引入干细胞领域,对于从结构特征的角度,在基因组尺度上理解干细胞的标志性分子和分化机理也具有一定的意义。我们的结果显示,干细胞和成熟细胞差异表达的基因在分子结构特征上存在差异;并且,在干细胞分化进程中经历结构变化的染色质片段,也可能与这些片段的GC含量有关。我们的这些结果,其深入意义还有待于进一步的研究和开掘。
The identification of the correlations between the molecular features of mammalian genes and their patterns of expression, as well as the exploration of the evolutionary processes of these molecular features are fundamental biological issues and remain subjects of controversy. Developmental processes are believed to be of critical importance to the investigation of evolutionary mechanisms. Moreover, stem cells, progenitor cells and their derivates, defined by their distinct differentiation potential, provide ideal models of the mammalian developmental hierarchy. Therefore, in this thesis, we tried to establish the correlations between the molecular features of mammalian genes and their patterns of expression, based on the developmental stage-related patterns of gene expression in models of mouse stem cell differentiation.
We established the correlations between the levels of gene expression and codon usage in different cell types. Our results showed that the optimal codons exhibited variation within the developmental hierarchy. Specifically, in certain mouse stem cells and progenitor cells in early developmental stages of ontogeny, the optimal codons were the AT-ending ones, while the mouse major codons are the GC-ending ones. We also found that genes that were enriched (developmental-pivotal genes, DPGs) or specifically expressed (developmental-specific genes, DSGs) at different developmental stages had different patterns of codon usage. Moreover, at the same developmental stage, DSGs generally used more GC-ending codons compared with DPGs. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons.
It has been indicated that codon usage (GC3) and local genomic GC content (GCg) are closely correlated in mammalian genome. Our results also showed that the variations of GCg were correlated with the developmental-stage related patterns of gene expression. We further investigated the distribution and organization of developmental stage-related genes in mouse chromosomes. We found that the distributions of genes corresponding to each developmental stage were not homogeneous among different chromosomes, suggesting the contributions of different chromosomes could be distinct at each developmental stage. We also observed that many developmental stage- related genes were organized as clusters in chromosomes. Moreover, genes within clusters generally used more GC-ending codons than genes out of the clusters.
By a comparative genomics approach, we further investigated the origin and the evolutionary processes of developmental stage-related genes. First, our data showed that the evolutionary rates of highly expressed genes were lower than that of mid-lowly expressed genes, indicating the influence of selective constraints on highly expressed genes was still detectable after the human-mouse and mouse-rat divergence. In contrast with these observations, DPGs and DSGs generally had higher evolutionary rates than non-developmental-pivotal genes (NDPGs). The higher rates might infer different functional constraints of these genes after the human-mouse and mouse–rat divergence. Second, we indicated that there were similar patterns of codon usage among orthologous genes of warm-blood vertebrates. These results suggested that the codon usage biases of mouse genes were formed in the common ancestor of warm-blood vertebrates. Third, we found highly expressed genes and NDPGs, compared with mid-lowly expressed genes and developmental-selectively expressed genes (DPGs and DSGs) respectively, could find more orthologous genes in genome of fruit fly. We also showed that both expression patterns and molecular features were correlated with the age of mouse genes.
The investigations above are dependent on the published high-throughput studies of stem cells and their derivates from ectoderm and mesoderm. We in turn to explore whether the codon usage, genomic GC content, gene distribution, and gene age are also correlated with the developmental stage- related patterns of gene expression in differentiation processes of endoderm. We defined a precursor cell population from adult mouse pancreas by selective culture. We found these precursor cells were located in the islets and around the pancreatic ducts. Based on the analyses of the expression profiling of both this pancreatic precursor cell population and mouse islets, our data showed that the molecular features, genomic characteristics and evolutionary processes are also correlated with developmental-stage related patterns of gene expression in endoderm, generally consistent with the observations in ectoderm and mesoderm.
Using the models of stem cell differentiation, the current study provides certain useful clues of evolutionary issues at the molecular level. For example, we showed new patterns of mammalian codon usage and new evidence of the presence of natural selection at mammalian synonymous sites. Moreover, our data also assist our understanding of the biological meaning of genomic GC content and the evolutionary processes of mammalian genes.
The current study has applied theoretical analyses of molecular evolution into stem cell research to gain a better understanding of stem cell differentiation at the genomic level. For example, we found that mammalian genes that specifically expressed at different developmental stages bear different molecular features. In addition, we also suggested that the genome segments that are involved in chromatin remodeling might correlate with their GC content. Further investigation will be needed to better understand the significance and implications of the findings presented here.
引文
1. Martin GR: Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 1981, 78:7634-7638.
2. Nagy A, Gocza E, Diaz EM, Prideaux VR, Ivanyi E, Markkula M, Rossant J: Embryonic stem cells alone are able to support fetal development in the mouse. Development 1990, 110:815-821.
3. Ying QL, Nichols J, Chambers I, Smith A: BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 2003, 115:281-292.
4. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science 1998, 282(5391):1145-1147.
5. Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD: Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci U S A 1998, 95(23):13726-13731.
6. Ying QL, Stavridis M, Griffiths D, Li M, Smith A: Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 2003, 21:183-186.
7. Burt RK, Verda L, Kim DA, Oyama Y, Luo K, Link C: Embryonic stem cells as an alternate marrow donor source: engraftment without graft-versus-host disease. J Exp Med 2004, 199:895-904.
8. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J: Identification of a neural stem cell in the adult mammalian central nervous system. Cell 1999, 96(1):25-34.
9. Chiasson BJ, Tropepe V, Morshead CM, van der Kooy D: Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J Neurosci 1999, 19(11):4462-4471.
10. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A: Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999, 97:703-716.
11. Nunes MC, Roy NS, Keyoung HM, Goodman RR, McKhann G, 2nd, Jiang L, Kang J, Nedergaard M, Goldman SA: Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 2003, 9(4):439-447.
12. Morshead CM, van der Kooy D: Disguising adult neural stem cells. Curr Opin Neurobiol 2004, 14(1):125-131.
13. McCulloch EA, Siminovitch L, Till JE: Spleen-Colony Formation in Anemic Mice of Genotype Ww. Science 1964, 144:844-846.
14. Bryder D, Rossi DJ, Weissman IL: Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 2006, 169(2):338-346.
15. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW: AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997, 90(12):5002-5012.
16. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N et al: Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005, 6(3):314-322.
17. Pomerantz J, Blau HM: Nuclear reprogramming: a key to stem cell function in regenerative medicine. Nat Cell Biol 2004, 6(9):810-816.
18. Kawase E, Yamazaki Y, Yagi T, Yanagimachi R, Pedersen RA: Mouse embryonic stem (ES) cell lines established from neuronal cell-derived cloned blastocysts. Genesis 2000, 28(3-4):156-163.
19. Munsie MJ, Michalska AE, O'Brien CM, Trounson AO, Pera MF, Mountford PS: Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol 2000, 10(16):989-992.
20. Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P: Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 2001, 292(5517):740-743.
21. Hochedlinger K, Jaenisch R: Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 2002, 415(6875):1035-1038.
22. Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R: Mice cloned from olfactory sensory neurons. Nature 2004, 428(6978):44-49.
23. Ng RK, Gurdon JB: Epigenetic memory of active gene transcription is inherited through somatic cell nuclear transfer. Proc Natl Acad Sci U S A 2005, 102(6):1957-1962.
24. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ: Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001, 105:369-377.
25. Moore MA: "Turning brain into blood"--clinical applications of stem-cell research in neurobiology and hematology. N Engl J Med 1999,
341(8):605-607.
26. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL: Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 1999, 283(5401):534-537.
27. Brazelton TR, Rossi FM, Keshet GI, Blau HM: From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000, 290(5497):1775-1779.
28. Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR: Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000, 290(5497):1779-1782.
29. Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, Belmonte N, Ferrari G, Leone BE, Bertuzzi F et al: Bone marrow mesenchymal stemcells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood 2005, 106(2):419-427.
30. Jackson KA, Mi T, Goodell MA: Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci U S A 1999, 96(25):14482-14486.
31. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP: Bone marrow as a potential source of hepatic oval cells. Science 1999, 284(5417):1168-1170.
32. Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS: Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 2000, 31(1):235-240.
33. Deng J, Steindler DA, Laywell ED, Petersen BE: Neural trans-differentiation potential of hepatic oval cells in the neonatal mouse brain. Exp Neurol 2003, 182(2):373-382.
34. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M: Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003, 422(6934):897-901.
35. Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS: Lack of a fusion requirement for development of bone marrow-derived epithelia. Science 2004, 305(5680):90-93.
36. Ying QL, Nichols J, Evans EP, Smith AG: Changing potency by spontaneous fusion. Nature 2002, 416(6880):545-548.
37. Wurmser AE, Gage FH: Stem cells: cell fusion causes confusion. Nature 2002, 416(6880):485-487.
38. Teratani T, Yamamoto H, Aoyagi K, Sasaki H, Asari A, Quinn G, Sasaki H, Terada M, Ochiya T: Direct hepatic fate specification from mouse embryonic stem cells. Hepatology 2005, 41(4):836-846.
39. Lian G, Wang C, Teng C, Zhang C, Du L, Zhong Q, Miao C, Ding M, Deng H: Failure of hepatocyte marker-expressing hematopoietic progenitor cells to efficiently convert into hepatocytes in vitro. Exp Hematol 2006, 34(3):348-358.
40. Hansson M, Tonning A, Frandsen U, Petri A, Rajagopal J, Englund MC, Heller RS, Hakansson J, Fleckner J, Skold HN et al: Artifactual insulin release from differentiated embryonic stem cells. Diabetes 2004, 53(10):2603-2609.
41. McKinney-Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA: Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci U S A 2002, 99(3):1341-1346.
42. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M et al: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002, 418(6893):41-49.
43. Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ et al: Regulation of neuronal traits by a novel transcriptional complex. Neuron 2001, 31:353-365.
44. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR: A stem cell molecular signature. Science 2002, 298:601-604.
45. Raff M: Adult stem cell plasticity: fact or artifact? Annu Rev Cell Dev Biol 2003, 19:1-22.
46. Wurmser AE, Nakashima K, Summers RG, Toni N, D'Amour KA, Lie DC, Gage FH: Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 2004, 430(6997):350-356.
47. Ianus A, Holz GG, Theise ND, Hussain MA: In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003, 111(6):843-850.
48. Hori Y, Gu X, Xie X, Kim SK: Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2005, 2(4):e103.
49. Oh SH, Muzzonigro TM, Bae SH, LaPlante JM, Hatch HM, Petersen BE: Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest 2004, 84(5):607-617.
50. Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 2004, 53(7):1721-1732.
51. Choi KS, Shin JS, Lee JJ, Kim YS, Kim SB, Kim CW: In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract. Biochem Biophys Res Commun 2005, 330(4):1299-1305.
52. Lechner A, Yang YG, Blacken RA, Wang L, Nolan AL, Habener JF: No evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo. Diabetes 2004, 53(3):616-623.
53. Choi JB, Uchino H, Azuma K, Iwashita N, Tanaka Y, Mochizuki H, Migita M, Shimada T, Kawamori R, Watada H: Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells. Diabetologia 2003, 46(10):1366-1374.
54. Di Gioacchino G, Di Campli C, Zocco MA, Piscaglia AC, Novi M, Santoro M, Santoliquido A, Flore R, Tondi P, Pola P et al: Transdifferentiation of stem cells in pancreatic cells: state of the art. Transplant Proc 2005, 37(6):2662-2663.
55. Tessem JS, DeGregori J: Roles for bone-marrow-derived cells in beta-cell maintenance. Trends Mol Med 2004, 10(11):558-564.
56. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ: SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005, 121(7):1109-1121.
57. Shi Y, Hou L, Tang F, Jiang W, Wang P, Ding M, Deng H: Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novelthree-step approach with activin A and all-trans retinoic acid. Stem Cells 2005, 23(5):656-662.
58. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE: Generation of a functional mammary gland from a single stem cell. Nature 2006, 439(7072):84-88.
59. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature 2006, 439(7079):993-997.
60. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D: Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004, 22(9):1115-1124.
61. Morrison SJ, Hemmati HD, Wandycz AM, Weissman IL: The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci U S A 1995, 92(22):10302-10306.
62. Morrison SJ, Weissman IL: The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1994, 1(8):661-673.
63. Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL: Identification of a lineage of multipotent hematopoietic progenitors. Development 1997, 124(10):1929-1939.
64. Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF: Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 2001, 412(6848):736-739.
65. Nagato M, Heike T, Kato T, Yamanaka Y, Yoshimoto M, Shimazaki T, Okano H, Nakahata T: Prospective characterization of neural stem cells by flow cytometry analysis using a combination of surface markers. J Neurosci Res 2005, 80(4):456-466.
66. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL: Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 2000, 97(26):14720-14725.
67. Milne HM, Burns CJ, Kitsou-Mylona I, Luther MJ, Minger SL, Persaud SJ, Jones PM: Generation of insulin-expressing cells from mouse embryonic stem cells. Biochem Biophys Res Commun 2005, 328(2):399-403.
68. Keller G: Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 2005, 19(10):1129-1155.
69. Ahlgren U, Jonsson J, Edlund H: The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 1996, 122(5):1409-1416.
70. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H: beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev 1998, 12(12):1763-1768.
71. Micallef SJ, Janes ME, Knezevic K, Davis RP, Elefanty AG, Stanley EG:Retinoic acid induces Pdx1-positive endoderm in differentiating mouse embryonic stem cells. Diabetes 2005, 54(2):301-305.
72. Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N et al: Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000, 6(5):568-572.
73. Tang DQ, Lu S, Sun YP, Rodrigues E, Chou W, Yang C, Cao LZ, Chang LJ, Yang LJ: Reprogramming liver-stem WB cells into functional insulin-producing cells by persistent expression of Pdx1- and Pdx1-VP16 mediated by lentiviral vectors. Lab Invest 2006, 86(1):83-93.
74. Cao LZ, Tang DQ, Horb ME, Li SW, Yang LJ: High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 2004, 53(12):3168-3178.
75. Lowell S: Stem cells in the genomic age. Genome Biol 2006, 7:315.
76. Van Hoof D, Mummery CL, Heck AJ, Krijgsveld J: Embryonic stem cell proteomics. Expert Rev Proteomics 2006, 3(4):427-437.
77. Bystrykh L, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang J, Manly KF et al: Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'. Nat Genet 2005, 37(3):225-232.
78. Shannon MF, Rao S: Transcription. Of chips and ChIPs. Science 2002, 296(5568):666-669.
79. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K et al: Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 2006, 125:301-313.
80. Dvash T, Mayshar Y, Darr H, McElhaney M, Barker D, Yanuka O, Kotkow KJ, Rubin LL, Benvenisty N, Eiges R: Temporal gene expression during differentiation of human embryonic stem cells and embryoid bodies. Hum Reprod 2004, 19(12):2875-2883.
81. Calhoun JD, Rao RR, Warrenfeltz S, Rekaya R, Dalton S, McDonald J, Stice SL: Transcriptional profiling of initial differentiation events in human embryonic stem cells. Biochem Biophys Res Commun 2004, 323(2):453-464.
82. Liu Y, Shin S, Zeng X, Zhan M, Gonzalez R, Mueller FJ, Schwartz CM, Xue H, Li H, Baker SC et al: Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Dev Biol 2006, 6:20.
83. Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K et al: Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat Biotechnol 2004, 22(6):707-716.
84. Boheler KR, Tarasov KV: SAGE analysis to identify embryonic stem cell-predominant transcripts. Methods Mol Biol 2006, 329:195-221.
85. Richards M, Tan SP, Tan JH, Chan WK, Bongso A: The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 2004, 22(1):51-64.
86. Richards M, Tan SP, Chan WK, Bongso A: Reverse serial analysis of gene expression (SAGE) characterization of orphan SAGE tags from human embryonic stem cells identifies the presence of novel transcripts and antisense transcription of key pluripotency genes. Stem Cells 2006, 24(5):1162-1173.
87. Bhattacharya B, Cai J, Luo Y, Miura T, Mejido J, Brimble SN, Zeng X, Schulz TC, Rao MS, Puri RK: Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies. BMC Dev Biol 2005, 5:22.
88. Rao M: Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells. Dev Biol 2004, 275:269-286.
89. Robson P: The maturing of the human embryonic stem cell transcriptome profile. Trends Biotechnol 2004, 22(12):609-612.
90. Gershon D: Microarray technology: an array of opportunities. Nature 2002, 416(6883):885-891.
91. Duret L: Evolution of synonymous codon usage in metazoans. Curr Opin Genet Dev 2002, 12:640-649.
92. Margulies EH, Kardia SL, Innis JW: Identification and prevention of a GC content bias in SAGE libraries. Nucleic Acids Res 2001, 29:E60-60.
93. Matsuzaki Y, Kinjo K, Mulligan RC, Okano H: Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity 2004, 20(1):87-93.
94. Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN et al: Genomic alterations in cultured human embryonic stem cells. Nat Genet 2005, 37(10):1099-1103.
95. Furusawa T, Ikeda M, Inoue F, Ohkoshi K, Hamano T, Tokunaga T: Gene Expression Profiling of Mouse Embryonic Stem Cell Subpopulations. Biol Reprod 2006.
96. Furusawa T, Ohkoshi K, Honda C, Takahashi S, Tokunaga T: Embryonic stem cells expressing both platelet endothelial cell adhesion molecule-1 and stage-specific embryonic antigen-1 differentiate predominantly into epiblast cells in a chimeric embryo. Biol Reprod 2004, 70(5):1452-1457.
97. Kurimoto K, Yabuta Y, Ohinata Y, Ono Y, Uno KD, Yamada RG, Ueda HR, Saitou M: An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis. Nucleic Acids Res 2006, 34(5):e42.
98. Chiang MK, Melton DA: Single-cell transcript analysis of pancreas development. Dev Cell 2003, 4(3):383-393.
99. Kelly DL, Rizzino A: DNA microarray analyses of genes regulated during the differentiation of embryonic stem cells. Mol Reprod Dev 2000, 56(2):113-123.
100. Tanaka TS, Kunath T, Kimber WL, Jaradat SA, Stagg CA, Usuda M, Yokota T, Niwa H, Rossant J, Ko MS: Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res 2002, 12(12):1921-1928.
101. Sperger JM, Chen X, Draper JS, Antosiewicz JE, Chon CH, Jones SB, Brooks JD, Andrews PW, Brown PO, Thomson JA: Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci U S A 2003, 100(23):13350-13355.
102. Palmqvist L, Glover CH, Hsu L, Lu M, Bossen B, Piret JM, Humphries RK, Helgason CD: Correlation of murine embryonic stem cell gene expression profiles with functional measures of pluripotency. Stem Cells 2005, 23(5):663-680.
103. Beqqali A, Kloots J, Ward-van Oostwaard D, Mummery C, Passier R: Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells 2006, 24(8):1956-1967.
104. Pritsker M, Ford NR, Jenq HT, Lemischka IR: Genomewide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells. Proc Natl Acad Sci U S A 2006, 103(18):6946-6951.
105. Park IK, He Y, Lin F, Laerum OD, Tian Q, Bumgarner R, Klug CA, Li K, Kuhr C, Doyle MJ et al: Differential gene expression profiling of adult murine hematopoietic stem cells. Blood 2002, 99(2):488-498.
106. Terskikh AV, Miyamoto T, Chang C, Diatchenko L, Weissman IL: Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 2003, 102(1):94-101.
107. Georgantas RW, 3rd, Tanadve V, Malehorn M, Heimfeld S, Chen C, Carr L, Martinez-Murillo F, Riggins G, Kowalski J, Civin CI: Microarray and serial analysis of gene expression analyses identify known and novel transcripts overexpressed in hematopoietic stem cells. Cancer Res 2004, 64(13):4434-4441.
108. Eckfeldt CE, Mendenhall EM, Flynn CM, Wang TF, Pickart MA, Grindle SM, Ekker SC, Verfaillie CM: Functional analysis of human hematopoietic stem cell gene expression using zebrafish. PLoS Biol 2005, 3(8):e254.
109. Huttmann A, Duhrsen U, Heydarian K, Klein-Hitpass L, Boes T, Boyd AW, Li CL: Gene expression profiles in murine hematopoietic stem cells revisited: analysis of cDNA libraries reveals high levels of translational and metabolic activities. Stem Cells 2006, 24(7):1719-1727.
110. Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL: From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci U S A 2001, 98(14):7934-7939.
111. Easterday MC, Dougherty JD, Jackson RL, Ou J, Nakano I, Paucar AA, Roobini B, Dianati M, Irvin DK, Weissman IL et al: Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations. Dev Biol 2003, 264(2):309-322.
112. Kim CG, Lee JJ, Jung DY, Jeon J, Heo HS, Kang HC, Shin JH, Cho YS, Cha KJ, Kim CG et al: Profiling of differentially expressed genes in human stem cells by cDNA microarray. Mol Cells 2006, 21(3):343-355.
113. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA: "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 2002, 298:597-600.
114. Fortunel NO, Otu HH, Ng HH, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA et al: Comment on " 'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science 2003, 302(5644):393; author reply 393.
115. Evsikov AV, Solter D: Comment on " 'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science 2003, 302(5644):393; author reply 393.
116. Vogel G: Stem cell research. Same results, different interpretations. Science 2003, 299(5605):324.
117. Giudice G: Conserved cellular and molecular mechanisms in development. Cell Biol Int 2001, 25(11):1081-1090.
118. Sato N, Sanjuan IM, Heke M, Uchida M, Naef F, Brivanlou AH: Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 2003, 260(2):404-413.
119. Cotsarelis G: Gene expression profiling gets to the root of human hair follicle stem cells. J Clin Invest 2006, 116(1):19-22.
120. Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB, Brady JN, Udey MC, Vogel JC: Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 2006, 116(1):249-260.
121. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E: Defining the epithelial stem cell niche in skin. Science 2004, 303(5656):359-363.
122. Christiano AM: Epithelial stem cells: stepping out of their niche. Cell 2004, 118(5):530-532.
123. Mitalipov S, Kuo HC, Byrne J, Clepper L, Meisner L, Johnson J, Zeier R, Wolf D: Isolation and Characterization of Novel Rhesus Monkey Embryonic Stem Cell Lines. Stem Cells 2006.
124. Byrne JA, Mitalipov SM, Clepper L, Wolf DP: Transcriptional Profiling of Rhesus Monkey Embryonic Stem Cells. Biol Reprod 2006.
125. Roloff TC, Nuber UA: Chromatin, epigenetics and stem cells. Eur J Cell Biol 2005, 84(2-3):123-135.
126. Peterson CL, Laniel MA: Histones and histone modifications. Curr Biol 2004, 14(14):R546-551.
127. Margueron R, Trojer P, Reinberg D: The key to development: interpreting the histone code? Curr Opin Genet Dev 2005, 15(2):163-176.
128. Jenuwein T, Allis CD: Translating the histone code. Science 2001, 293(5532):1074-1080.
129. Kubicek S, Schotta G, Lachner M, Sengupta R, Kohlmaier A, Perez-Burgos L, Linderson Y, Martens JH, O'Sullivan RJ, Fodor BD et al: The role of histone modifications in epigenetic transitions during normal and perturbed development. Ernst Schering Res Found Workshop 2006(57):1-27.
130. Santos-Rosa H, Caldas C: Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 2005, 41(16):2381-2402.
131. de la Serna IL, Ohkawa Y, Imbalzano AN: Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nat Rev Genet 2006, 7(6):461-473.
132. Song MR, Ghosh A: FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat Neurosci 2004, 7:229-235.
133. Ajamian F, Suuronen T, Salminen A, Reeben M: Upregulation of class II histone deacetylases mRNA during neural differentiation of cultured rat hippocampal progenitor cells. Neurosci Lett 2003, 346:57-60.
134. Rasmussen TP: Embryonic stem cell differentiation: a chromatin perspective. Reprod Biol Endocrinol 2003, 1:100.
135. Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M et al: Chromatin signatures of pluripotent cell lines. Nat Cell Biol 2006, 8(5):532-538.
136. Szutorisz H, Canzonetta C, Georgiou A, Chow CM, Tora L, Dillon N: Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol Cell Biol 2005, 25(5):1804-1820.
137. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK et al: Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006, 441(7091):349-353.
138. Orkin SH: Chipping away at the embryonic stem cell network. Cell 2005, 122(6):828-830.
139. Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J et al: The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 2006, 38(4):431-440.
140. Buszczak M, Spradling AC: Searching chromatin for stem cell identity. Cell 2006, 125(2):233-236.
141. Squazzo SL, O'Geen H, Komashko VM, Krig SR, Jin VX, Jang SW, Margueron R, Reinberg D, Green R, Farnham PJ: Suz12 binds to silenced regions of the genome in a cell-type-specific manner. Genome Res 2006, 16(7):890-900.
142. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K et al: A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 2006, 125(2):315-326.
143. Kaji K, Caballero IM, MacLeod R, Nichols J, Wilson VA, Hendrich B: The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 2006, 8(3):285-292.
144. Wang X, Ge S, Gonzalez I, McNamara G, Rountree CB, Xi KK, Huang G, Bhushan A, Crooks GM: Formation of pancreatic duct epithelium from bone marrow during neonatal development. Stem Cells 2006, 24(2):307-314.
145. Bibikova M, Chudin E, Wu B, Zhou L, Garcia EW, Liu Y, Shin S, Plaia TW, Auerbach JM, Arking DE et al: Human embryonic stem cells have a unique epigenetic signature. Genome Res 2006, 16(9):1075-1083.
146. Okusaka T, Matsumura Y, Aoki K: New approaches for pancreatic cancer in Japan. Cancer Chemother Pharmacol 2004, 54 Suppl 1:S78-82.
147. Shen Y, Chow J, Wang Z, Fan G: Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells. Hum Mol Genet 2006, 15(17):2623-2635.
148. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF: Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003, 423(6937):302-305.
149. Lessard J, Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003, 423(6937):255-260.
150. Akala OO, Clarke MF: Hematopoietic stem cell self-renewal. Curr Opin Genet Dev 2006.
151. Kunisato A, Chiba S, Nakagami-Yamaguchi E, Kumano K, Saito T, Masuda S, Yamaguchi T, Osawa M, Kageyama R, Nakauchi H et al: HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo. Blood 2003, 101(5):1777-1783.
152. Iwama A, Oguro H, Negishi M, Kato Y, Nakauchia H: Epigenetic regulation of hematopoietic stem cell self-renewal by polycomb group genes. Int J Hematol 2005, 81(4):294-300.
153. Cao R, Tsukada Y, Zhang Y: Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 2005, 20(6):845-854.
154. Kamminga LM, Bystrykh LV, de Boer A, Houwer S, Douma J, Weersing E, Dontje B, de Haan G: The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 2006, 107(5):2170-2179.
155. Nemeth MJ, Kirby MR, Bodine DM: Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and differentiation. Proc Natl Acad Sci U S A 2006.
156. Georgopoulos K: Haematopoietic cell-fate decisions, chromatin regulation and ikaros. Nat Rev Immunol 2002, 2(3):162-174.
157. Lopez RA, Schoetz S, DeAngelis K, O'Neill D, Bank A: Multiple hematopoietic defects and delayed globin switching in Ikaros null mice. Proc Natl Acad Sci U S A 2002, 99(2):602-607.
158. Cobb BS, Smale ST: Ikaros-family proteins: in search of molecular functions during lymphocyte development. Curr Top Microbiol Immunol2005, 290:29-47.
159. Kondo T: Epigenetic alchemy for cell fate conversion. Curr Opin Genet Dev 2006, 16(5):502-507.
160. Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G et al: Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 2002, 298(5599):1747-1752.
161. Lunyak VV, Rosenfeld MG: No rest for REST: REST/NRSF regulation of neurogenesis. Cell 2005, 121(4):499-501.
162. Su X, Gopalakrishnan V, Stearns D, Aldape K, Lang FF, Fuller G, Snyder E, Eberhart CG, Majumder S: Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Mol Cell Biol 2006, 26(5):1666-1678.
163. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH: A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 2004, 116(6):779-793.
164. Fleitz J, Rumelhart S, Goldman F, Ambruso D, Sokol RJ, Pacini D, Quinones R, Holida M, Lee N, Tannous R et al: Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond syndrome. Bone Marrow Transplant 2002, 29(1):75-79.
165. Matsumoto S, Banine F, Struve J, Xing R, Adams C, Liu Y, Metzger D, Chambon P, Rao MS, Sherman LS: Brg1 is required for murine neural stem cell maintenance and gliogenesis. Dev Biol 2006, 289(2):372-383.
166. Schmittwolf C, Kirchhof N, Jauch A, Durr M, Harder F, Zenke M, Muller AM: In vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents. Embo J 2005, 24(3):554-566.
167. Araki H, Mahmud N, Milhem M, Nunez R, Xu M, Beam CA, Hoffman R: Expansion of human umbilical cord blood SCID-repopulating cells using chromatin-modifying agents. Exp Hematol 2006, 34(2):140-149.
168. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
169. Bernardi G: Isochores and the evolutionary genomics of vertebrates. Gene 2000, 241:3-17.
170. Kosak ST, Groudine M: Gene order and dynamic domains. Science 2004, 306(5696):644-647.
171. Kosak ST, Groudine M: Form follows function: The genomic organization of cellular differentiation. Genes Dev 2004, 18:1371-1384.
172. Vinogradov AE: Noncoding DNA, isochores and gene expression: nucleosome formation potential. Nucleic Acids Res 2005, 33:559-563.
173. Vinogradov AE: DNA helix: the importance of being GC-rich. Nucleic Acids Res 2003, 31:1838-1844.
174. Hiratani I, Leskovar A, Gilbert DM: Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A 2004,101:16861-16866.
175. Zhou J, Liu WJ, Peng SW, Sun XY, Frazer I: Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability. J Virol 1999, 73:4972-4982.
176. Kudla G, Lipinski L, Caffin F, Helwak A, Zylicz M: High guanine and cytosine content increases mRNA levels in mammalian cells. PLoS Biol 2006, 4:e180.
177. Li H, Liu Y, Shin S, Sun Y, Loring JF, Mattson MP, Rao MS, Zhan M: Transcriptome coexpression map of human embryonic stem cells. BMC Genomics 2006, 7:103.
178. Gilbert SF: The morphogenesis of evolutionary developmental biology. Int J Dev Biol 2003, 47:467-477.
179. Arthur W: The emerging conceptual framework of evolutionary developmental biology. Nature 2002, 415:757-764.
180. Hall BK: Evo-Devo: evolutionary developmental mechanisms. Int J Dev Biol 2003, 47(7-8):491-495.
181. Garcia-Fernandez J: The genesis and evolution of homeobox gene clusters. Nat Rev Genet 2005, 6(12):881-892.
182. Chang CC, Cook CE: Trends in genomic 'evo-devo'. Genome Biol 2002, 3:REPORTS4019.
183. Ponger L, Duret L, Mouchiroud D: Determinants of CpG islands: expression in early embryo and isochore structure. Genome Res 2001, 11:1854-1860.
184. Castillo-Davis CI, Hartl DL: Genome evolution and developmental constraint in Caenorhabditis elegans. Mol Biol Evol 2002, 19:728-735.
185. Gothert JR, Gustin SE, Hall MA, Green AR, Gottgens B, Izon DJ, Begley CG: In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis. Blood 2005, 105:2724-2732.
1. Duret L: Evolution of synonymous codon usage in metazoans. Curr Opin Genet Dev 2002, 12:640-649.
2. Gouy M, Gautier C: Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res 1982, 10:7055-7074.
3. Sharp PM, Li WH: An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol 1986, 24:28-38.
4. Sharp PM, Tuohy TM, Mosurski KR: Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res 1986, 14:5125-5143.
5. Coghlan A, Wolfe KH: Relationship of codon bias to mRNA concentration and protein length in Saccharomyces cerevisiae. Yeast 2000, 16:1131-1145.
6. Akashi H: Gene expression and molecular evolution. Curr Opin Genet Dev 2001, 11:660-666.
7. Stenico M, Lloyd AT, Sharp PM: Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases. Nucleic Acids Res 1994, 22:2437-2446.
8. Moriyama EN, Powell JR: Codon usage bias and tRNA abundance in Drosophila. J Mol Evol 1997, 45:514-523.
9. Powell JR, Moriyama EN: Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A 1997, 94:7784-7790.
10. Duret L, Mouchiroud D: Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci U S A 1999, 96:4482-4487.
11. Dong H, Nilsson L, Kurland CG: Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J Mol Biol 1996, 260:649-663.
12. Akashi H, Eyre-Walker A: Translational selection and molecular evolution. Curr Opin Genet Dev 1998, 8:688-693.
13. Kanaya S, Yamada Y, Kinouchi M, Kudo Y, Ikemura T: Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessed by multivariate analysis. J Mol Evol 2001, 53:290-298.
14. Duret L: tRNA gene number and codon usage in the C. elegans genome are co-adapted for optimal translation of highly expressed genes. Trends Genet 2000, 16:287-289.
15. Bulmer M: The selection-mutation-drift theory of synonymous codon usage. Genetics 1991, 129:897-907.
16. Semon M, Mouchiroud D, Duret L: Relationship between gene expression and GC-content in mammals: statistical significance and biological relevance. Hum Mol Genet 2005, 14:421-427.
17. Konu O, Li MD: Correlations between mRNA expression levels and GC contents of coding and untranslated regions of genes in rodents. J MolEvol 2002, 54:35-41.
18. Vinogradov AE: Isochores and tissue-specificity. Nucleic Acids Res 2003, 31:5212-5220.
19. Urrutia AO, Hurst LD: The signature of selection mediated by expression on human genes. Genome Res 2003, 13:2260-2264.
20. Comeron JM: Selective and mutational patterns associated with gene expression in humans: influences on synonymous composition and intron presence. Genetics 2004, 167:1293-1304.
21. Margulies EH, Kardia SL, Innis JW: Identification and prevention of a GC content bias in SAGE libraries. Nucleic Acids Res 2001, 29:E60-60.
22. DeBry RW, Marzluff WF: Selection on silent sites in the rodent H3 histone gene family. Genetics 1994, 138:191-202.
23. Mouchiroud D, Fichant G, Bernardi G: Compositional compartmentalization and gene composition in the genome of vertebrates. J Mol Evol 1987, 26:198-204.
24. Bernardi G: The isochore organization of the human genome and its evolutionary history--a review. Gene 1993, 135:57-66.
25. Bernardi G: The human genome: organization and evolutionary history. Annu Rev Genet 1995, 29:445-476.
26. Pesole G, Bernardi G, Saccone C: Isochore specificity of AUG initiator context of human genes. FEBS Lett 1999, 464:60-62.
27. Lercher MJ, Urrutia AO, Pavlicek A, Hurst LD: A unification of mosaic structures in the human genome. Hum Mol Genet 2003, 12:2411-2415.
28. Ponger L, Duret L, Mouchiroud D: Determinants of CpG islands: expression in early embryo and isochore structure. Genome Res 2001, 11:1854-1860.
29. Goncalves I, Duret L, Mouchiroud D: Nature and structure of human genes that generate retropseudogenes. Genome Res 2000, 10:672-678.
30. D'Onofrio G: Expression patterns and gene distribution in the human genome. Gene 2002, 300:155-160.
31. Zhang L, Li WH: Mammalian housekeeping genes evolve more slowly than tissue-specific genes. Mol Biol Evol 2004, 21:236-239.
32. Plotkin JB, Robins H, Levine AJ: Tissue-specific codon usage and the expression of human genes. Proc Natl Acad Sci U S A 2004, 101:12588-12591.
33. Semon M, Lobry JR, Duret L: No evidence for tissue-specific adaptation of synonymous codon usage in humans. Mol Biol Evol 2006, 23:523-529.
34. Wolfe KH, Sharp PM, Li WH: Mutation rates differ among regions of the mammalian genome. Nature 1989, 337:283-285.
35. Eyre-Walker AC: An analysis of codon usage in mammals: selection or mutation bias? J Mol Evol 1991, 33:442-449.
36. Sharp PM, Averof M, Lloyd AT, Matassi G, Peden JF: DNA sequence evolution: the sounds of silence. Philos Trans R Soc Lond B Biol Sci 1995, 349:241-247.
37. Hughes AL, Yeager M: Comparative evolutionary rates of introns and exons in murine rodents. J Mol Evol 1997, 45:125-130.
38. Francino MP, Ochman H: Isochores result from mutation not selection. Nature 1999, 400:30-31.
39. Castillo-Davis CI, Mekhedov SL, Hartl DL, Koonin EV, Kondrashov FA: Selection for short introns in highly expressed genes. Nat Genet 2002, 31:415-418.
40. Eyre-Walker A: Evidence of selection on silent site base composition in mammals: potential implications for the evolution of isochores and junk DNA. Genetics 1999, 152:675-683.
41. Hurst LD, Pal C: Evidence for purifying selection acting on silent sites in BRCA1. Trends Genet 2001, 17:62-65.
42. Hellmann I, Zollner S, Enard W, Ebersberger I, Nickel B, Paabo S: Selection on human genes as revealed by comparisons to chimpanzee cDNA. Genome Res 2003, 13:831-837.
43. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21:1014-1023.
44. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21(6):1014-1023.
45. Schattner P, Diekhans M: Regions of extreme synonymous codon selection in mammalian genes. Nucleic Acids Res 2006, 34:1700-1710.
46. Chamary JV, Parmley JL, Hurst LD: Hearing silence: non-neutral evolution at synonymous sites in mammals. Nat Rev Genet 2006, 7:98-108.
47. Vinogradov AE: Noncoding DNA, isochores and gene expression: nucleosome formation potential. Nucleic Acids Res 2005, 33:559-563.
48. Vinogradov AE: DNA helix: the importance of being GC-rich. Nucleic Acids Res 2003, 31:1838-1844.
49. Parmley JL, Chamary JV, Hurst LD: Evidence for purifying selection against synonymous mutations in mammalian exonic splicing enhancers. Mol Biol Evol 2006, 23:301-309.
50. Willie E, Majewski J: Evidence for codon bias selection at the pre-mRNA level in eukaryotes. Trends Genet 2004, 20:534-538.
51. Chamary JV, Hurst LD: Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals. Genome Biol 2005, 6:R75.
52. Lavner Y, Kotlar D: Codon bias as a factor in regulating expression via translation rate in the human genome. Gene 2005, 345:127-138.
53. Comeron JM: Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans. Proc Natl Acad Sci U S A 2006, 103:6940-6945.
54. Oresic M, Dehn M, Korenblum D, Shalloway D: Tracing specific synonymous codon-secondary structure correlations through evolution. JMol Evol 2003, 56:473-484.
55. Archetti M: Selection on codon usage for error minimization at the protein level. J Mol Evol 2004, 59:400-415.
56. Musto H, Cruveiller S, D'Onofrio G, Romero H, Bernardi G: Translational selection on codon usage in Xenopus laevis. Mol Biol Evol 2001, 18:1703-1707.
57. Romero H, Zavala A, Musto H, Bernardi G: The influence of translational selection on codon usage in fishes from the family Cyprinidae. Gene 2003, 317:141-147.
58. Fryxell KJ, Zuckerkandl E: Cytosine deamination plays a primary role in the evolution of mammalian isochores. Mol Biol Evol 2000, 17:1371-1383.
59. Francino MP, Ochman H: Deamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences. Mol Biol Evol 2001, 18:1147-1150.
60. Green P, Ewing B, Miller W, Thomas PJ, Green ED: Transcription-associated mutational asymmetry in mammalian evolution. Nat Genet 2003, 33:514-517.
61. Iida K, Akashi H: A test of translational selection at 'silent' sites in the human genome: base composition comparisons in alternatively spliced genes. Gene 2000, 261:93-105.
62. Smith NG, Hurst LD: The effect of tandem substitutions on the correlation between synonymous and nonsynonymous rates in rodents. Genetics 1999, 153:1395-1402.
63. Bielawski JP, Dunn KA, Yang Z: Rates of nucleotide substitution and mammalian nuclear gene evolution. Approximate and maximum-likelihood methods lead to different conclusions. Genetics 2000, 156:1299-1308.
64. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
65. Chen FC, Wang SS, Chen CJ, Li WH, Chuang TJ: Alternatively and Constitutively Spliced Exons Are Subject to Different Evolutionary Forces. Mol Biol Evol 2006, 23:675-682.
66. Fullerton SM, Bernardo Carvalho A, Clark AG: Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 2001, 18:1139-1142.
67. Galtier N, Piganeau G, Mouchiroud D, Duret L: GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 2001, 159:907-911.
68. Galtier N: Gene conversion drives GC content evolution in mammalian histones. Trends Genet 2003, 19:65-68.
69. Meunier J, Duret L: Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 2004, 21:984-990.
70. Montoya-Burgos JI, Boursot P, Galtier N: Recombination explains isochores in mammalian genomes. Trends Genet 2003, 19:128-130.
71. Nickoloff JA: Transcription enhances intrachromosomal homologous recombination in mammalian cells. Mol Cell Biol 1992, 12:5311-5318.
72. Droge P: Transcription-driven site-specific DNA recombination in vitro. Proc Natl Acad Sci U S A 1993, 90:2759-2763.
73. Nicolas A: Relationship between transcription and initiation of meiotic recombination: toward chromatin accessibility. Proc Natl Acad Sci U S A 1998, 95:87-89.
74. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA: "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 2002, 298:597-600.
75. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR: A stem cell molecular signature. Science 2002, 298:601-604.
76. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A et al: Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A 2002, 99:4465-4470.
77. Sharp PM, Tuohy TM, Mosurski KR: Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res 1986, 14(13):5125-5143.
78. Duret L, Mouchiroud D: Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol Biol Evol 2000, 17:68-74.
79. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al: Initial sequencing and analysis of the human genome. Nature 2001, 409(6822):860-921.
80. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P et al: Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420(6915):520-562.
81. Agris PF: Decoding the genome: a modified view. Nucleic Acids Res 2004, 32:223-238.
82. Murphy FVt, Ramakrishnan V, Malkiewicz A, Agris PF: The role of modifications in codon discrimination by tRNA(Lys)UUU. Nat Struct Mol Biol 2004, 11:1186-1191.
83. Tong KL, Wong JT: Anticodon and wobble evolution. Gene 2004, 333:169-177.
84. Umeda N, Suzuki T, Yukawa M, Ohya Y, Shindo H, Watanabe K: Mitochondria-specific RNA-modifying enzymes responsible for the biosynthesis of the wobble base in mitochondrial tRNAs. Implications for the molecular pathogenesis of human mitochondrial diseases. J Biol Chem 2005, 280:1613-1624.
85. Ikemura T: Codon usage and tRNA content in unicellular and multicellular organisms. Mol Biol Evol 1985, 2:13-34.
86. White BN, Tener GM, Holden J, Suzuki DT: Analysis of tRNAs during the development of Drosophila. Dev Biol 1973, 33:185-195.
87. Hosbach HA, Kubli E: Transfer RNA in aging Drosophila: II. Isoacceptor patterns. Mech Ageing Dev 1979, 10:141-149.
88. Beutler E, Gelbart T, Han JH, Koziol JA, Beutler B: Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage. Proc Natl Acad Sci U S A 1989, 86(1):192-196.
89. Karlin S, Mrazek J: What drives codon choices in human genes? J Mol Biol 1996, 262(4):459-472.
90. Stryer L: Biochemistry, 4 edn. USA; 1995.
91. Rinkevich B: A critical approach to the definition of Darwinian units of selection. Biol Bull 2000, 199(3):231-240.
92. Weissman IL: Stem cells: units of development, units of regeneration, and units in evolution. Cell 2000, 100:157-168.
93. Stoner DS, Rinkevich B, Weissman IL: Heritable germ and somatic cell lineage competitions in chimeric colonial protochordates. Proc Natl Acad Sci U S A 1999, 96(16):9148-9153.
94. Laird DJ, De Tomaso AW, Weissman IL: Stem cells are units of natural selection in a colonial ascidian. Cell 2005, 123:1351-1360.
95. Rinkevich B: The colonial urochordate Botryllus schlosseri: from stem cells and natural tissue transplantation to issues in evolutionary ecology. Bioessays 2002, 24(8):730-740.
96. Mayr WR, Pausch V, Schnedl W: Human chimaera detectable only by investigation of her progeny. Nature 1979, 277(5693):210-211.
97. Calabrese P, Tavare S, Shibata D: Pretumor progression: clonal evolution of human stem cell populations. Am J Pathol 2004, 164(4):1337-1346.
98. Clarke MF, Fuller M: Stem cells and cancer: two faces of eve. Cell 2006, 124:1111-1115.
99. Huntly BJ, Gilliland DG: Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 2005, 5:311-321.
1. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
2. Bernardi G: Isochores and the evolutionary genomics of vertebrates. Gene 2000, 241:3-17.
3. Bernardi G, Olofsson B, Filipski J, Zerial M, Salinas J, Cuny G, Meunier-Rotival M, Rodier F: The mosaic genome of warm-blooded vertebrates. Science 1985, 228:953-958.
4. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al: Initial sequencing and analysis of the human genome. Nature 2001, 409(6822):860-921.
5. Hurst LD, Pal C, Lercher MJ: The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet 2004, 5(4):299-310.
6. Clay O, Carels N, Douady C, Macaya G, Bernardi G: Compositional heterogeneity within and among isochores in mammalian genomes. I. CsCl and sequence analyses. Gene 2001, 276(1-2):15-24.
7. Macaya G, Thiery JP, Bernardi G: An approach to the organization of eukaryotic genomes at a macromolecular level. J Mol Biol 1976, 108(1):237-254.
8. Haring D, Kypr J: No isochores in the human chromosomes 21 and 22? Biochem Biophys Res Commun 2001, 280(2):567-573.
9. Clay O, Bernardi G: The isochores in human chromosomes 21 and 22. Biochem Biophys Res Commun 2001, 285(4):855-856.
10. Bernardi G: Misunderstandings about isochores. Part 1. Gene 2001, 276(1-2):3-13.
11. Pavlicek A, Clay O, Jabbari K, Paces J, Bernardi G: Isochore conservation between MHC regions on human chromosome 6 and mouse chromosome
17. FEBS Lett 2002, 511(1-3):175-177.
12. Li W: Are isochore sequences homogeneous? Gene 2002, 300(1-2):129-139.
13. Li W, Bernaola-Galvan P, Carpena P, Oliver JL: Isochores merit the prefix 'iso'. Comput Biol Chem 2003, 27(1):5-10.
14. Li W: Delineating relative homogeneous G+C domains in DNA sequences. Gene 2001, 276(1-2):57-72.
15. Cohen N, Dagan T, Stone L, Graur D: GC composition of the human genome: in search of isochores. Mol Biol Evol 2005, 22(5):1260-1272.
16. Clay O, Bernardi G: How not to search for isochores: a reply to Cohen et Al. Mol Biol Evol 2005, 22(12):2315-2317.
17. Finishing the euchromatic sequence of the human genome. Nature 2004, 431(7011):931-945.
18. Costantini M, Clay O, Auletta F, Bernardi G: An isochore map of human chromosomes. Genome Res 2006, 16(4):536-541.
19. Zhang CT, Wang J, Zhang R: A novel method to calculate the G+C content of genomic DNA sequences. J Biomol Struct Dyn 2001, 19(2):333-341.
20. Zhang CT, Zhang R: Analysis of distribution of bases in the coding sequences by a diagrammatic technique. Nucleic Acids Res 1991, 19(22):6313-6317.
21. Zhang R, Zhang CT: Z curves, an intutive tool for visualizing and analyzing the DNA sequences. J Biomol Struct Dyn 1994, 11(4):767-782.
22. Zhang CT, Zhang R: An isochore map of the human genome based on the Z curve method. Gene 2003, 317(1-2):127-135.
23. Zhang CT, Zhang R: Isochore structures in the mouse genome. Genomics 2004, 83(3):384-394.
24. Gao F, Zhang CT: Isochore structures in the chicken genome. Febs J 2006, 273(8):1637-1648.
25. Zhang R, Zhang CT: Isochore structures in the genome of the plant Arabidopsis thaliana. J Mol Evol 2004, 59(2):227-238.
26. Gao F, Zhang CT: GC-Profile: a web-based tool for visualizing and analyzing the variation of GC content in genomic sequences. Nucleic Acids Res 2006, 34(Web Server issue):W686-691.
27. Fryxell KJ, Zuckerkandl E: Cytosine deamination plays a primary role in the evolution of mammalian isochores. Mol Biol Evol 2000, 17:1371-1383.
28. Francino MP, Ochman H: Deamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences. Mol Biol Evol 2001, 18:1147-1150.
29. Green P, Ewing B, Miller W, Thomas PJ, Green ED: Transcription-associated mutational asymmetry in mammalian evolution. Nat Genet 2003, 33:514-517.
30. Wolfe KH, Sharp PM, Li WH: Mutation rates differ among regions of the mammalian genome. Nature 1989, 337:283-285.
31. Francino MP, Ochman H: Isochores result from mutation not selection. Nature 1999, 400:30-31.
32. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21(6):1014-1023.
33. Alvarez-Valin F, Lamolle G, Bernardi G: Isochores, GC3 and mutation biases in the human genome. Gene 2002, 300(1-2):161-168.
34. Belle EM, Smith N, Eyre-Walker A: Analysis of the phylogenetic distribution of isochores in vertebrates and a test of the thermal stability hypothesis. J Mol Evol 2002, 55(3):356-363.
35. Hughes S, Zelus D, Mouchiroud D: Warm-blooded isochore structure in Nile crocodile and turtle. Mol Biol Evol 1999, 16(11):1521-1527.
36. Hurst LD, Merchant AR: High guanine-cytosine content is not an adaptation to high temperature: a comparative analysis amongst prokaryotes. Proc Biol Sci 2001, 268(1466):493-497.
37. Galtier N, Lobry JR: Relationships between genomic G+C content, RNA secondary structures, and optimal growth temperature in prokaryotes. J Mol Evol 1997, 44(6):632-636.
38. Jabbari K, Bernardi G: Body temperature and evolutionary genomics of vertebrates: a lesson from the genomes of Takifugu rubripes and Tetraodon nigroviridis. Gene 2004, 333:179-181.
39. Musto H, Naya H, Zavala A, Romero H, Alvarez-Valin F, Bernardi G: Genomic GC level, optimal growth temperature, and genome size in prokaryotes. Biochem Biophys Res Commun 2006, 347(1):1-3.
40. Galtier N, Piganeau G, Mouchiroud D, Duret L: GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 2001, 159:907-911.
41. Meunier J, Duret L: Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 2004, 21:984-990.
42. Montoya-Burgos JI, Boursot P, Galtier N: Recombination explains isochores in mammalian genomes. Trends Genet 2003, 19:128-130.
43. Galtier N: Gene conversion drives GC content evolution in mammalian histones. Trends Genet 2003, 19:65-68.
44. Fullerton SM, Bernardo Carvalho A, Clark AG: Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 2001, 18:1139-1142.
45. Belle EM, Duret L, Galtier N, Eyre-Walker A: The decline of isochores in mammals: an assessment of the GC content variation along the mammalian phylogeny. J Mol Evol 2004, 58(6):653-660.
46. Duret L, Semon M, Piganeau G, Mouchiroud D, Galtier N: Vanishing GC-rich isochores in mammalian genomes. Genetics 2002, 162(4):1837-1847.
47. Webster MT, Axelsson E, Ellegren H: Strong regional biases in nucleotide substitution in the chicken genome. Mol Biol Evol 2006, 23(6):1203-1216.
48. Arndt PF, Petrov DA, Hwa T: Distinct changes of genomic biases in nucleotide substitution at the time of Mammalian radiation. Mol Biol Evol 2003, 20(11):1887-1896.
49. Lercher MJ, Smith NG, Eyre-Walker A, Hurst LD: The evolution of isochores: evidence from SNP frequency distributions. Genetics 2002, 162(4):1805-1810.
50. Alvarez-Valin F, Clay O, Cruveiller S, Bernardi G: Inaccurate reconstruction of ancestral GC levels creates a "vanishing isochores" effect. Mol Phylogenet Evol 2004, 31(2):788-793.
51. Hackenberg M, Bernaola-Galvan P, Carpena P, Oliver JL: The biased distribution of Alus in human isochores might be driven by recombination. J Mol Evol 2005, 60(3):365-377.
52. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P et al: Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420(6915):520-562.
53. Kruglyak S, Tang H: Regulation of adjacent yeast genes. Trends Genet 2000, 16(3):109-111.
54. Lercher MJ, Urrutia AO, Hurst LD: Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 2002, 31(2):180-183.
55. Birnbaum K, Shasha DE, Wang JY, Jung JW, Lambert GM, Galbraith DW, Benfey PN: A gene expression map of the Arabidopsis root. Science 2003, 302(5652):1956-1960.
56. Spellman PT, Rubin GM: Evidence for large domains of similarly expressed genes in the Drosophila genome. J Biol 2002, 1(1):5.
57. Boutanaev AM, Kalmykova AI, Shevelyov YY, Nurminsky DI: Large clusters of co-expressed genes in the Drosophila genome. Nature 2002, 420(6916):666-669.
58. Parisi M, Nuttall R, Edwards P, Minor J, Naiman D, Lu J, Doctolero M, Vainer M, Chan C, Malley J et al: A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol 2004, 5(6):R40.
59. Stolc V, Gauhar Z, Mason C, Halasz G, van Batenburg MF, Rifkin SA, Hua S, Herreman T, Tongprasit W, Barbano PE et al: A gene expression map for the euchromatic genome of Drosophila melanogaster. Science 2004, 306(5696):655-660.
60. Garcia-Fernandez J: The genesis and evolution of homeobox gene clusters. Nat Rev Genet 2005, 6(12):881-892.
61. Ko MS, Threat TA, Wang X, Horton JH, Cui Y, Wang X, Pryor E, Paris J, Wells-Smith J, Kitchen JR et al: Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome. Hum Mol Genet 1998, 7(12):1967-1978.
62. Reymond A, Marigo V, Yaylaoglu MB, Leoni A, Ucla C, Scamuffa N, Caccioppoli C, Dermitzakis ET, Lyle R, Banfi S et al: Human chromosome 21 gene expression atlas in the mouse. Nature 2002, 420(6915):582-586.
63. Bortoluzzi S, Rampoldi L, Simionati B, Zimbello R, Barbon A, d'Alessi F, Tiso N, Pallavicini A, Toppo S, Cannata N et al: A comprehensive, high-resolution genomic transcript map of human skeletal muscle. Genome Res 1998, 8(8):817-825.
64. Versteeg R, van Schaik BD, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, van Kampen AH: The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Res 2003, 13:1998-2004.
65. Lercher MJ, Urrutia AO, Pavlicek A, Hurst LD: A unification of mosaic structures in the human genome. Hum Mol Genet 2003, 12:2411-2415.
66. Versteeg R, van Schaik BD, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, van Kampen AH: The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Res2003, 13(9):1998-2004.
67. Megy K, Audic S, Claverie JM: Positional clustering of differentially expressed genes on human chromosomes 20, 21 and 22. Genome Biol 2003, 4(2):P1.
68. Wei CL, Miura T, Robson P, Lim SK, Xu XQ, Lee MY, Gupta S, Stanton L, Luo Y, Schmitt J et al: Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells 2005, 23(2):166-185.
69. Pallavicini A, Zimbello R, Tiso N, Muraro T, Rampoldi L, Bortoluzzi S, Valle G, Lanfranchi G, Danieli GA: The preliminary transcript map of a human skeletal muscle. Hum Mol Genet 1997, 6(9):1445-1450.
70. Silver LM: The peculiar journey of a selfish chromosome: mouse t haplotypes and meiotic drive. Trends Genet 1993, 9(7):250-254.
71. Papaioannou VE, Silver LM: The T-box gene family. Bioessays 1998, 20(1):9-19.
72. Vogel JH, von Heydebreck A, Purmann A, Sperling S: Chromosomal clustering of a human transcriptome reveals regulatory background. BMC Bioinformatics 2005, 6:230.
73. Lercher MJ, Urrutia AO, Hurst LD: Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 2002, 31:180-183.
74. Li Q, Lee BT, Zhang L: Genome-scale analysis of positional clustering of mouse testis-specific genes. BMC Genomics 2005, 6(1):7.
75. Divina P, Vlcek C, Strnad P, Paces V, Forejt J: Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order. BMC Genomics 2005, 6(1):29.
76. Paillisson A, Dade S, Callebaut I, Bontoux M, Dalbies-Tran R, Vaiman D, Monget P: Identification, characterization and metagenome analysis of oocyte-specific genes organized in clusters in the mouse genome. BMC Genomics 2005, 6(1):76.
77. Yamashita T, Honda M, Takatori H, Nishino R, Hoshino N, Kaneko S: Genome-wide transcriptome mapping analysis identifies organ-specific gene expression patterns along human chromosomes. Genomics 2004, 84(5):867-875.
78. Yin YB, Zhang Y, Yu P, Luo JC, Jiang Y, Li SG: Comparative study of apoptosis-related gene loci in human, mouse and rat genomes. Acta Biochim Biophys Sin (Shanghai) 2005, 37(5):341-348.
79. Miller MA, Cutter AD, Yamamoto I, Ward S, Greenstein D: Clustered organization of reproductive genes in the C. elegans genome. Curr Biol 2004, 14(14):1284-1290.
80. Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, Paigen K: Evidence of a large-scale functional organization of mammalian chromosomes. PLoS Genet 2005, 1(3):e33.
81. Johnnidis JB, Venanzi ES, Taxman DJ, Ting JP, Benoist CO, Mathis DJ:Chromosomal clustering of genes controlled by the aire transcription factor. Proc Natl Acad Sci U S A 2005, 102(20):7233-7238.
82. Lee JM, Sonnhammer EL: Genomic gene clustering analysis of pathways in eukaryotes. Genome Res 2003, 13(5):875-882.
83. Allocco DJ, Kohane IS, Butte AJ: Quantifying the relationship between co-expression, co-regulation and gene function. BMC Bioinformatics 2004, 5:18.
84. Yanai I, Korbel JO, Boue S, McWeeney SK, Bork P, Lercher MJ: Similar gene expression profiles do not imply similar tissue functions. Trends Genet 2006, 22(3):132-138.
85. Hurst LD, Lercher MJ: Unusual linkage patterns of ligands and their cognate receptors indicate a novel reason for non-random gene order in the human genome. BMC Evol Biol 2005, 5:62.
86. Singer GA, Lloyd AT, Huminiecki LB, Wolfe KH: Clusters of co-expressed genes in mammalian genomes are conserved by natural selection. Mol Biol Evol 2005, 22(3):767-775.
87. Semon M, Lobry JR, Duret L: No evidence for tissue-specific adaptation of synonymous codon usage in humans. Mol Biol Evol 2006, 23:523-529.
88. Kosak ST, Groudine M: Gene order and dynamic domains. Science 2004, 306(5696):644-647.
89. Kosak ST, Groudine M: Form follows function: The genomic organization of cellular differentiation. Genes Dev 2004, 18(12):1371-1384.
90. Kalmykova AI, Nurminsky DI, Ryzhov DV, Shevelyov YY: Regulated chromatin domain comprising cluster of co-expressed genes in Drosophila melanogaster. Nucleic Acids Res 2005, 33(5):1435-1444.
91. Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J, Li L: Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood 2003, 101:383-389.
92. Kanaya S, Yamada Y, Kinouchi M, Kudo Y, Ikemura T: Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessed by multivariate analysis. J Mol Evol 2001, 53:290-298.
93. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA: "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 2002, 298:597-600.
94. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR: A stem cell molecular signature. Science 2002, 298:601-604.
95. Kosak ST, Groudine M: Form follows function: The genomic organization of cellular differentiation. Genes Dev 2004, 18:1371-1384.
96. Ajamian F, Suuronen T, Salminen A, Reeben M: Upregulation of class II histone deacetylases mRNA during neural differentiation of cultured rat hippocampal progenitor cells. Neurosci Lett 2003, 346:57-60.
97. Rasmussen TP: Embryonic stem cell differentiation: a chromatinperspective. Reprod Biol Endocrinol 2003, 1:100.
98. Lee JH, Hart SR, Skalnik DG: Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis 2004, 38:32-38.
99. Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ et al: Regulation of neuronal traits by a novel transcriptional complex. Neuron 2001, 31:353-365.
100. Takizawa T, Nakashima K, Namihira M, Ochiai W, Uemura A, Yanagisawa M, Fujita N, Nakao M, Taga T: DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell 2001, 1:749-758.
101. Song MR, Ghosh A: FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat Neurosci 2004, 7:229-235.
102. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH: A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 2004, 116:779-793.
103. Vinogradov AE: Noncoding DNA, isochores and gene expression: nucleosome formation potential. Nucleic Acids Res 2005, 33:559-563.
104. Bernardi G: The isochore organization of the human genome and its evolutionary history--a review. Gene 1993, 135:57-66.
105. Bernardi G: The human genome: organization and evolutionary history. Annu Rev Genet 1995, 29:445-476.
106. Vinogradov AE: Isochores and tissue-specificity. Nucleic Acids Res 2003, 31:5212-5220.
107. Hiratani I, Leskovar A, Gilbert DM: Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A 2004,
101:16861-16866.
1. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D: Ultraconserved elements in the human genome. Science 2004, 304(5675):1321-1325.
2. Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S et al: Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 2005, 15(8):1034-1050.
3. Fitch WM: Distinguishing homologous from analogous proteins. Syst Zool 1970, 19(2):99-113.
4. Koonin EV, Mushegian AR, Bork P: Non-orthologous gene displacement. Trends Genet 1996, 12(9):334-336.
5. Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH: Role of duplicate genes in genetic robustness against null mutations. Nature 2003, 421(6918):63-66.
6. Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H et al: Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 1999, 285(5429):901-906.
7. Gibson TJ, Spring J: Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding multidomain proteins. Trends Genet 1998, 14(2):46-49; discussion 49-50.
8. Tatusov RL, Koonin EV, Lipman DJ: A genomic perspective on protein families. Science 1997, 278(5338):631-637.
9. Tatusov RL, Galperin MY, Natale DA, Koonin EV: The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res 2000, 28(1):33-36.
10. Dessimoz C, Boeckmann B, Roth AC, Gonnet GH: Detecting non-orthology in the COGs database and other approaches grouping orthologs using genome-specific best hits. Nucleic Acids Res 2006, 34(11):3309-3316.
11. Rao M: Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells. Dev Biol 2004, 275:269-286.
12. Hoegg S, Meyer A: Hox clusters as models for vertebrate genome evolution. Trends Genet 2005, 21(8):421-424.
13. Li WH, Yang J, Gu X: Expression divergence between duplicate genes. Trends Genet 2005, 21(11):602-607.
14. Planet PJ: Tree disagreement: measuring and testing incongruence in phylogenies. J Biomed Inform 2006, 39(1):86-102.
15. Horiike T, Hamada K, Kanaya S, Shinozawa T: Origin of eukaryotic cell nuclei by symbiosis of Archaea in Bacteria is revealed by homology-hit analysis. Nat Cell Biol 2001, 3(2):210-214.
16. Noda AO, Ikeo K, Gojobori T: Comparative genome analyses of nervous system-specific genes. Gene 2006, 365:130-136.
17. Masatoshi Nei SK: Molecular Evolution and Phylogenetics: Oxford University Press, Inc.; 2000.
18. Kimura M: On the probability of fixation of mutant genes in a population. Genetics 1962, 47:713-719.
19. Wen-Hsiung Li DG: Fundamentals of Molecular Evolution. Sunderland Massachusetts: Sinauer Associates, INC. Publisher; 1991.
20. Kimura M: Evolutionary rate at the molecular level. Nature 1968, 217:624-626.
21. Chamary JV, Parmley JL, Hurst LD: Hearing silence: non-neutral evolution at synonymous sites in mammals. Nat Rev Genet 2006, 7:98-108.
22. Miyata T, Hayashida H: Extraordinarily high evolutionary rate of pseudogenes: evidence for the presence of selective pressure against changes between synonymous codons. Proc Natl Acad Sci U S A 1981, 78(9):5739-5743.
23. Nei M, Gojobori T: Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 1986, 3:418-426.
24. Pamilo P, Bianchi NO: Evolution of the Zfx and Zfy genes: rates and interdependence between the genes. Mol Biol Evol 1993, 10(2):271-281.
25. Comeron JM: A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J Mol Evol 1995, 41(6):1152-1159.
26. Muse SV: Estimating synonymous and nonsynonymous substitution rates. Mol Biol Evol 1996, 13(1):105-114.
27. Feng DF, Doolittle RF: Converting amino acid alignment scores into measures of evolutionary time: a simulation study of various relationships. J Mol Evol 1997, 44(4):361-370.
28. Grishin NV: Estimation of the number of amino acid substitutions per site when the aubatitution rate varies among sites. J Mol Evol 1995, 41:675-679.
29. Fraser HB, Hirsh AE, Steinmetz LM, Scharfe C, Feldman MW: Evolutionary rate in the protein interaction network. Science 2002, 296(5568):750-752.
30. Wilson AC, Carlson SS, White TJ: Biochemical evolution. Annu Rev Biochem 1977, 46:573-639.
31. Hurst LD, Smith NG: Do essential genes evolve slowly? Curr Biol 1999, 9(14):747-750.
32. Hurst LD, Williams EJ: Covariation of GC content and the silent site substitution rate in rodents: implications for methodology and for the evolution of isochores. Gene 2000, 261:107-114.
33. Smith NG, Hurst LD: The effect of tandem substitutions on the correlation between synonymous and nonsynonymous rates in rodents. Genetics 1999, 153:1395-1402.
34. Duret L, Mouchiroud D: Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol Biol Evol 2000, 17:68-74.
35. Wolfe KH, Sharp PM: Mammalian gene evolution: nucleotide sequence divergence between mouse and rat. J Mol Evol 1993, 37:441-456.
36. Kimura M, Ota T: On some principles governing molecular evolution. Proc Natl Acad Sci U S A 1974, 71(7):2848-2852.
37. Hirsh AE, Fraser HB: Protein dispensability and rate of evolution. Nature 2001, 411(6841):1046-1049.
38. Yang J, Gu Z, Li WH: Rate of protein evolution versus fitness effect of gene deletion. Mol Biol Evol 2003, 20(5):772-774.
39. Castillo-Davis CI, Hartl DL: Conservation, relocation and duplication in genome evolution. Trends Genet 2003, 19(11):593-597.
40. Pal C, Papp B, Hurst LD: Highly expressed genes in yeast evolve slowly. Genetics 2001, 158:927-931.
41. Subramanian S, Kumar S: Gene expression intensity shapes evolutionary rates of the proteins encoded by the vertebrate genome. Genetics 2004, 168:373-381.
42. Zhang L, Li WH: Mammalian housekeeping genes evolve more slowly than tissue-specific genes. Mol Biol Evol 2004, 21:236-239.
43. Krylov DM, Wolf YI, Rogozin IB, Koonin EV: Gene loss, protein sequence divergence, gene dispensability, expression level, and interactivity are correlated in eukaryotic evolution. Genome Res 2003, 13:2229-2235.
44. Pal C, Papp B, Hurst LD: Genomic function: Rate of evolution and gene dispensability. Nature 2003, 421(6922):496-497; discussion 497-498.
45. Jordan IK, Rogozin IB, Wolf YI, Koonin EV: Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res 2002, 12(6):962-968.
46. Rocha EP, Danchin A: An analysis of determinants of amino acids substitution rates in bacterial proteins. Mol Biol Evol 2004, 21(1):108-116.
47. Zhang J, He X: Significant impact of protein dispensability on the instantaneous rate of protein evolution. Mol Biol Evol 2005, 22(4):1147-1155.
48. Fraser HB, Wall DP, Hirsh AE: A simple dependence between protein evolution rate and the number of protein-protein interactions. BMC Evol Biol 2003, 3:11.
49. Jordan IK, Wolf YI, Koonin EV: No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly. BMC Evol Biol 2003, 3:1.
50. Walker DR, Koonin EV: SEALS: a system for easy analysis of lots of sequences. Proc Int Conf Intell Syst Mol Biol 1997, 5:333-339.
51. Koski LB, Golding GB: The closest BLAST hit is often not the nearest neighbor. J Mol Evol 2001, 52(6):540-542.
52. Bloom JD, Adami C: Apparent dependence of protein evolutionary rate on number of interactions is linked to biases in protein-protein interactions data sets. BMC Evol Biol 2003, 3:21.
53. Bloom JD, Adami C: Evolutionary rate depends on number ofprotein-protein interactions independently of gene expression level: response. BMC Evol Biol 2004, 4:14.
54. Fraser HB, Hirsh AE: Evolutionary rate depends on number of protein-protein interactions independently of gene expression level. BMC Evol Biol 2004, 4:13.
55. Saeed R, Deane CM: Protein protein interactions, evolutionary rate, abundance and age. BMC Bioinformatics 2006, 7:128.
56. Kuma K, Iwabe N, Miyata T: Functional constraints against variations on molecules from the tissue level: slowly evolving brain-specific genes demonstrated by protein kinase and immunoglobulin supergene families. Mol Biol Evol 1995, 12(1):123-130.
57. Wyckoff GJ, Wang W, Wu CI: Rapid evolution of male reproductive genes in the descent of man. Nature 2000, 403(6767):304-309.
58. Panhuis TM, Swanson WJ: Molecular evolution and population genetic analysis of candidate female reproductive genes in Drosophila. Genetics 2006, 173(4):2039-2047.
59. Hurst LD, Ellegren H: Sex biases in the mutation rate. Trends Genet 1998, 14(11):446-452.
60. Comeron JM: Selective and mutational patterns associated with gene expression in humans: influences on synonymous composition and intron presence. Genetics 2004, 167:1293-1304.
61. Doolittle RF, Feng DF, Johnson MS, McClure MA: Relationships of human protein sequences to those of other organisms. Cold Spring Harb Symp Quant Biol 1986, 51 Pt 1:447-455.
62. Alba MM, Castresana J: Inverse relationship between evolutionary rate and age of mammalian genes. Mol Biol Evol 2005, 22(3):598-606.
63. Elhaik E, Sabath N, Graur D: The "inverse relationship between evolutionary rate and age of mammalian genes" is an artifact of increased genetic distance with rate of evolution and time of divergence. Mol Biol Evol 2006, 23(1):1-3.
64. Fischer D, Eisenberg D: Finding families for genomic ORFans. Bioinformatics 1999, 15(9):759-762.
65. Dujon B: The yeast genome project: what did we learn? Trends Genet 1996, 12(7):263-270.
66. Cai JJ, Woo PC, Lau SK, Smith DK, Yuen KY: Accelerated evolutionary rate may be responsible for the emergence of lineage-specific genes in ascomycota. J Mol Evol 2006, 63(1):1-11.
67. Domazet-Loso T, Tautz D: An evolutionary analysis of orphan genes in Drosophila. Genome Res 2003, 13(10):2213-2219.
68. Daubin V, Ochman H: Bacterial genomes as new gene homes: the genealogy of ORFans in E. coli. Genome Res 2004, 14(6):1036-1042.
69. Drummond DA, Raval A, Wilke CO: A single determinant dominates the rate of yeast protein evolution. Mol Biol Evol 2006, 23(2):327-337.
70. McInerney JO: The causes of protein evolutionary rate variation. TrendsEcol Evol 2006, 21(5):230-232.
71. Wyckoff GJ, Malcom CM, Vallender EJ, Lahn BT: A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate. Trends Genet 2005, 21(7):381-385.
72. Hurst LD, Pal C: Evidence for purifying selection acting on silent sites in BRCA1. Trends Genet 2001, 17:62-65.
73. Xing Y, Lee C: Can RNA selection pressure distort the measurement of Ka/Ks? Gene 2006, 370:1-5.
74. Hellmann I, Zollner S, Enard W, Ebersberger I, Nickel B, Paabo S: Selection on human genes as revealed by comparisons to chimpanzee cDNA. Genome Res 2003, 13:831-837.
75. Smith NG, Hurst LD: Sensitivity of patterns of molecular evolution to alterations in methodology: a critique of Hughes and Yeager. J Mol Evol 1998, 47(4):493-500.
76. Chen FC, Vallender EJ, Wang H, Tzeng CS, Li WH: Genomic divergence between human and chimpanzee estimated from large-scale alignments of genomic sequences. J Hered 2001, 92(6):481-489.
77. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21:1014-1023.
78. Hughes AL, Yeager M: Comparative evolutionary rates of introns and exons in murine rodents. J Mol Evol 1997, 45:125-130.
79. Subramanian S, Kumar S: Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes. Genome Res 2003, 13(5):838-844.
80. Chen FC, Li WH: Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am J Hum Genet 2001, 68(2):444-456.
81. Lu J, Wu CI: Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee. Proc Natl Acad Sci U S A 2005, 102(11):4063-4067.
82. Smith NG, Hurst LD: The causes of synonymous rate variation in the rodent genome. Can substitution rates be used to estimate the sex bias in mutation rate? Genetics 1999, 152(2):661-673.
83. Keightley PD, Gaffney DJ: Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents. Proc Natl Acad Sci U S A 2003, 100(23):13402-13406.
84. Majewski J, Ott J: Distribution and characterization of regulatory elements in the human genome. Genome Res 2002, 12(12):1827-1836.
85. Bustamante CD, Nielsen R, Hartl DL: A maximum likelihood method for analyzing pseudogene evolution: implications for silent site evolution in humans and rodents. Mol Biol Evol 2002, 19(1):110-117.
86. Wolfe KH, Sharp PM, Li WH: Mutation rates differ among regions of the mammalian genome. Nature 1989, 337:283-285.
87. Matassi G, Sharp PM, Gautier C: Chromosomal location effects on gene sequence evolution in mammals. Curr Biol 1999, 9(15):786-791.
88. Hurst LD, Pal C, Lercher MJ: The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet 2004, 5(4):299-310.
89. Kumar S, Subramanian S: Mutation rates in mammalian genomes. Proc Natl Acad Sci U S A 2002, 99(2):803-808.
90. Casane D, Boissinot S, Chang BH, Shimmin LC, Li W: Mutation pattern variation among regions of the primate genome. J Mol Evol 1997, 45(3):216-226.
91. Nachman MW, Crowell SL: Estimate of the mutation rate per nucleotide in humans. Genetics 2000, 156(1):297-304.
92. Podlaha O, Zhang J: Nonneutral evolution of the transcribed pseudogene Makorin1-p1 in mice. Mol Biol Evol 2004, 21(12):2202-2209.
93. Fullerton SM, Bernardo Carvalho A, Clark AG: Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 2001, 18:1139-1142.
94. Galtier N, Piganeau G, Mouchiroud D, Duret L: GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 2001, 159:907-911.
95. Galtier N: Gene conversion drives GC content evolution in mammalian histones. Trends Genet 2003, 19:65-68.
96. Meunier J, Duret L: Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 2004, 21:984-990.
97. Montoya-Burgos JI, Boursot P, Galtier N: Recombination explains isochores in mammalian genomes. Trends Genet 2003, 19:128-130.
98. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
99. Bernardi G: Isochores and the evolutionary genomics of vertebrates. Gene 2000, 241:3-17.
100. Chen FC, Wang SS, Chen CJ, Li WH, Chuang TJ: Alternatively and Constitutively Spliced Exons Are Subject to Different Evolutionary Forces. Mol Biol Evol 2006, 23:675-682.
101. Yang Z: PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 1997, 13:555-556.
102. Sharp PM, Li WH: The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. Mol Biol Evol 1987, 4:222-230.
103. Sharp PM, Li WH: On the rate of DNA sequence evolution in Drosophila. J Mol Evol 1989, 28:398-402.
104. Shields DC, Sharp PM, Higgins DG, Wright F: "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol 1988, 5:704-716.
105. Powell JR, Moriyama EN: Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A 1997, 94:7784-7790.
106. Ureta-Vidal A, L. Ettwiller, et al. : Comparative genomics: Genome-wide analysis in metazoan eukaryotes. Nat Rev Genet 2003, 4(4):251-262.
1. Bertuzzi F, Marzorati S, Secchi A: Islet cell transplantation. Curr Mol Med 2006, 6(4):369-374.
2. Slack JM: Developmental biology of the pancreas. Development 1995, 121(6):1569-1580.
3. D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE: Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006.
4. Shi Y, Hou L, Tang F, Jiang W, Wang P, Ding M, Deng H: Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid. Stem Cells 2005, 23(5):656-662.
5. Narushima M, Kobayashi N, Okitsu T, Tanaka Y, Li SA, Chen Y, Miki A, Tanaka K, Nakaji S, Takei K et al: A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol 2005, 23(10):1274-1282.
6. Choi KS, Shin JS, Lee JJ, Kim YS, Kim SB, Kim CW: In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract. Biochem Biophys Res Commun 2005, 330(4):1299-1305.
7. Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 2004, 53(7):1721-1732.
8. Moriscot C, de Fraipont F, Richard MJ, Marchand M, Savatier P, Bosco D, Favrot M, Benhamou PY: Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells 2005, 23(4):594-603.
9. Deutsch G, Jung J, Zheng M, Lora J, Zaret KS: A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 2001, 128(6):871-881.
10. Burke Z, Oliver G: Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mech Dev 2002, 118(1-2):147-155.
11. Dabeva MD, Hurston E, Sharitz DA: Transcription factor and liver-specific mRNA expression in facultative epithelial progenitor cells of liver and pancreas. Am J Pathol 1995, 147(6):1633-1648.
12. Grompe M: Pancreatic-hepatic switches in vivo. Mech Dev 2003, 120(1):99-106.
13. Tosh D, Shen CN, Alison MR, Sarraf CE, Slack JM: Copper-deprivation in rats induces islet hyperplasia and hepatic metaplasia in the pancreas. Biol Cell 2006.
14. Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N et al: Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000, 6(5):568-572.
15. Cao LZ, Tang DQ, Horb ME, Li SW, Yang LJ: High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 2004, 53(12):3168-3178.
16. Zalzman M, Anker-Kitai L, Efrat S: Differentiation of human liver-derived, insulin-producing cells toward the beta-cell phenotype. Diabetes 2005, 54(9):2568-2575.
17. Drucker DJ: Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 2003, 17(2):161-171.
18. Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV: The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002, 32(1):128-134.
19. Hori Y, Gu X, Xie X, Kim SK: Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2005, 2(4):e103.
20. Shi CM, Cheng TM: Differentiation of dermis-derived multipotent cells into insulin-producing pancreatic cells in vitro. World J Gastroenterol 2004, 10(17):2550-2552.
21. Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller B, Vallejo M, Thomas MK, Habener JF: Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001, 50(3):521-533.
22. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D: Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004, 22(9):1115-1124.
23. Suzuki A, Oyama K, Fukao K, Nakauchi H, Taniguchi H: Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells. Cell Transplant 2002, 11(5):451-453.
24. Suzuki A, Nakauchi H, Taniguchi H: Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 2004, 53(8):2143-2152.
25. Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG: Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 2000, 6(3):278-282.
26. Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O'Neil JJ: In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 2000, 97(14):7999-8004.
27. Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca SY, Aye T, Sharma A: The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr Diabetes 2004, 5 Suppl 2:16-22.
28. Todorov I, Nair I, Ferreri K, Rawson J, Kuroda A, Pascual M, Omori K, Valiente L, Orr C, Al-Abdullah I et al: Multipotent progenitor cells isolated from adult human pancreatic tissue. Transplant Proc 2005, 37(8):3420-3421.
29. Beattie GM, Otonkoski T, Lopez AD, Hayek A: Functional beta-cell mass after transplantation of human fetal pancreatic cells: differentiation or proliferation? Diabetes 1997, 46(2):244-248.
30. Hayek A, Beattie GM: Experimental transplantation of human fetal and adult pancreatic islets. J Clin Endocrinol Metab 1997, 82(8):2471-2475.
31. Beattie GM, Lopez AD, Otonkoski T, Hayek A: Transplantation of human fetal pancreas: fresh vs. cultured fetal islets or ICCS. J Mol Med 1999, 77(1):70-73.
32. Hayek A: In search of endocrine progenitor/stem cells in the human pancreas. Pediatr Diabetes 2004, 5 Suppl 2:70-74.
33. Hayek A: Cell replacement in type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2005, 18 Suppl 1:1157-1161.
34. Huang H, Tang X: Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest 2003, 83(4):539-547.
35. Zhang L, Hong TP, Hu J, Liu YN, Wu YH, Li LS: Nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J Gastroenterol 2005, 11(19):2906-2911.
36. Maria-Engler SS, Correa-Giannella ML, Labriola L, Krogh K, Colin C, Lojudice FH, Aita CA, de Oliveira EM, Correa TC, da Silva IC et al: Co-localization of nestin and insulin and expression of islet cell markers in long-term human pancreatic nestin-positive cell cultures. J Endocrinol 2004, 183(3):455-467.
37. Abraham EJ, Kodama S, Lin JC, Ubeda M, Faustman DL, Habener JF: Human pancreatic islet-derived progenitor cell engraftment in immunocompetent mice. Am J Pathol 2004, 164(3):817-830.
38. Choi Y, Ta M, Atouf F, Lumelsky N: Adult pancreas generates multipotent stem cells and pancreatic and nonpancreatic progeny. Stem Cells 2004, 22(6):1070-1084.
39. Weir GC, Bonner-Weir S: Beta-cell precursors--a work in progress. Nat Biotechnol 2004, 22(9):1095-1096.
40. Yamamoto T, Yamato E, Taniguchi H, Shimoda M, Tashiro F, Hosoi M, Sato T, Fujii S, Miyazaki JI: Stimulation of cAMP signalling allows isolation of clonal pancreatic precursor cells from adult mouse pancreas. Diabetologia 2006, 49(10):2359-2367.
41. Dor Y, Brown J, Martinez OI, Melton DA: Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004, 429(6987):41-46.
42. Levine F, Mercola M: No pancreatic endocrine stem cells? N Engl J Med2004, 351(10):1024-1026.
43. Wang X, Hu J, Zhao D, Wang G, Tan L, Du L, Yang J, Hou L, Zhang H, Yu Y et al: NestinnegCD24low/- population from fetal Nestin-EGFP transgenic mice enriches the pancreatic endocrine progenitor cells. Pancreas 2005, 31(4):385-391.
44. Treutelaar MK, Skidmore JM, Dias-Leme CL, Hara M, Zhang L, Simeone D, Martin DM, Burant CF: Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet. Diabetes 2003, 52(10):2503-2512.
45. Delacour A, Nepote V, Trumpp A, Herrera PL: Nestin expression in pancreatic exocrine cell lineages. Mech Dev 2004, 121(1):3-14.
46. Street CN, Lakey JR, Seeberger K, Helms L, Rajotte RV, Shapiro AM, Korbutt GS: Heterogenous expression of nestin in human pancreatic tissue precludes its use as an islet precursor marker. J Endocrinol 2004, 180(2):213-225.
47. Selander L, Edlund H: Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev 2002, 113(2):189-192.
48. Klein T, Ling Z, Heimberg H, Madsen OD, Heller RS, Serup P: Nestin is expressed in vascular endothelial cells in the adult human pancreas. J Histochem Cytochem 2003, 51(6):697-706.
49. Gu G, Brown JR, Melton DA: Direct lineage tracing reveals the ontogeny of pancreatic cell fates during mouse embryogenesis. Mech Dev 2003, 120(1):35-43.
50. Gu G, Dubauskaite J, Melton DA: Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002, 129(10):2447-2457.
51. Laconi E, Oren R, Mukhopadhyay DK, Hurston E, Laconi S, Pani P, Dabeva MD, Shafritz DA: Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol 1998, 153(1):319-329.
52. Guo D, Fu T, Nelson JA, Superina RA, Soriano HE: Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride. Transplantation 2002, 73(11):1818-1824.
53. Petersen BE, Zajac VF, Michalopoulos GK: Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 1998, 27(4):1030-1038.
54. Sell S: Heterogeneity and plasticity of hepatocyte lineage cells. Hepatology 2001, 33(3):738-750.
55. Beattie GM, Cirulli V, Lopez AD, Hayek A: Ex vivo expansion of human pancreatic endocrine cells. J Clin Endocrinol Metab 1997, 82(6):1852-1856.
56. Gao R, Ustinov J, Korsgren O, Otonkoski T: In vitro neogenesis of human islets reflects the plasticity of differentiated human pancreatic cells. Diabetologia 2005, 48(11):2296-2304.
57. Lechner A, Nolan AL, Blacken RA, Habener JF: Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue. Biochem Biophys Res Commun 2005, 327(2):581-588.
58. Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM: Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 2004, 306(5705):2261-2264.
59. Eberhardt M, Salmon P, von Mach MA, Hengstler JG, Brulport M, Linscheid P, Seboek D, Oberholzer J, Barbero A, Martin I et al: Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem Biophys Res Commun 2006, 345(3):1167-1176.
60. Gershengorn MC, Geras-Raaka E, Hardikar AA, Raaka BM: Are better islet cell precursors generated by epithelial-to-mesenchymal transition? Cell Cycle 2005, 4(3):380-382.
61. Duvillie B, Attali M, Aiello V, Quemeneur E, Scharfmann R: Label-retaining cells in the rat pancreas: location and differentiation potential in vitro. Diabetes 2003, 52(8):2035-2042.
62. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A: Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999, 97(6):703-716.
63. Dahlstrand J, Zimmerman LB, McKay RD, Lendahl U: Characterization of the human nestin gene reveals a close evolutionary relationship to neurofilaments. J Cell Sci 1992, 103 ( Pt 2):589-597.
64. Lendahl U, Zimmerman LB, McKay RD: CNS stem cells express a new class of intermediate filament protein. Cell 1990, 60(4):585-595.
65. Hunziker E, Stein M: Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem Biophys Res Commun 2000, 271(1):116-119.
66. Zhang L, Hu J, Hong TP, Liu YN, Wu YH, Li LS: Monoclonal side population progenitors isolated from human fetal pancreas. Biochem Biophys Res Commun 2005, 333(2):603-608.
67. Lechner A, Leech CA, Abraham EJ, Nolan AL, Habener JF: Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter. Biochem Biophys Res Commun 2002, 293(2):670-674.
68. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E: Defining the epithelial stem cell niche in skin. Science 2004, 303(5656):359-363.
69. Al-Abdullah IH, Ayala T, Panigrahi D, Kumar RM, Kumar MS: Neogenesis of pancreatic endocrine cells in copper-deprived rat models. Pancreas 2000, 21(1):63-68.
70. Waguri M, Yamamoto K, Miyagawa JI, Tochino Y, Yamamori K, Kajimoto Y, Nakajima H, Watada H, Yoshiuchi I, Itoh N et al: Demonstration of two different processes of beta-cell regeneration in a new diabetic mouse model induced by selective perfusion of alloxan. Diabetes 1997,46(8):1281-1290.
71. Lee CS, De Leon DD, Kaestner KH, Stoffers DA: Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3. Diabetes 2006, 55(2):269-272.
72. Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE: A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes 1993, 42(12):1715-1720.
73. Beattie GM, Levine F, Mally MI, Otonkoski T, O'Brien JS, Salomon DR, Hayek A: Acid beta-galactosidase: a developmentally regulated marker of endocrine cell precursors in the human fetal pancreas. J Clin Endocrinol Metab 1994, 78(5):1232-1240.
74. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J: Identification of a neural stem cell in the adult mammalian central nervous system. Cell 1999, 96(1):25-34.
75. Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD: Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 2001, 3(9):778-784.
76. Fernandes KJ, McKenzie IA, Mill P, Smith KM, Akhavan M, Barnabe-Heider F, Biernaskie J, Junek A, Kobayashi NR, Toma JG et al: A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol 2004, 6(11):1082-1093.
77. Tropepe V, Sibilia M, Ciruna BG, Rossant J, Wagner EF, van der Kooy D: Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev Biol 1999, 208(1):166-188.
78. Lammert E, Brown J, Melton DA: Notch gene expression during pancreatic organogenesis. Mech Dev 2000, 94(1-2):199-203.
79. Lee KM, Yasuda H, Hollingsworth MA, Ouellette MM: Notch 2-positive progenitors with the intrinsic ability to give rise to pancreatic ductal cells. Lab Invest 2005, 85(8):1003-1012.
80. Katoh M, Katoh M: Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells. Int J Mol Med 2006, 17(4):681-685.
81. Murtaugh LC, Stanger BZ, Kwan KM, Melton DA: Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 2003, 100(25):14920-14925.
82. Apelqvist A, Li H, Sommer L, Beatus P, Anderson DJ, Honjo T, Hrabe de Angelis M, Lendahl U, Edlund H: Notch signalling controls pancreatic cell differentiation. Nature 1999, 400(6747):877-881.
83. Fujikura J, Hosoda K, Iwakura H, Tomita T, Noguchi M, Masuzaki H, Tanigaki K, Yabe D, Honjo T, Nakao K: Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas. Cell Metab 2006, 3(1):59-65.
84. Chenn A, Walsh CA: Regulation of cerebral cortical size by control of cellcycle exit in neural precursors. Science 2002, 297(5580):365-369.
85. Zechner D, Fujita Y, Hulsken J, Muller T, Walther I, Taketo MM, Crenshaw EB, 3rd, Birchmeier W, Birchmeier C: beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol 2003, 258(2):406-418.
86. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N et al: Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005, 6(3):314-322.
87. Trowbridge JJ, Xenocostas A, Moon RT, Bhatia M: Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation. Nat Med 2006, 12(1):89-98.
88. Trowbridge JJ, Moon RT, Bhatia M: Hematopoietic stem cell biology: too much of a Wnt thing. Nat Immunol 2006, 7(10):1021-1023.
89. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R et al: GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol 2003, 10(12):1255-1266.
90. Klein PS, Melton DA: A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 1996, 93(16):8455-8459.
91. Coghlan MP, Culbert AA, Cross DA, Corcoran SL, Yates JW, Pearce NJ, Rausch OL, Murphy GJ, Carter PS, Roxbee Cox L et al: Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol 2000, 7(10):793-803.
92. Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF: Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 2001, 412(6848):736-739.
93. Murayama A, Matsuzaki Y, Kawaguchi A, Shimazaki T, Okano H: Flow cytometric analysis of neural stem cells in the developing and adult mouse brain. J Neurosci Res 2002, 69(6):837-847.
94. Inada A, Nienaber C, Bonner-Weir S: Endogenous beta-galactosidase expression in murine pancreatic islets. Diabetologia 2006, 49(5):1120-1122.
95. Gothot A, van der Loo JC, Clapp DW, Srour EF: Cell cycle-related changes in repopulating capacity of human mobilized peripheral blood CD34(+) cells in non-obese diabetic/severe combined immune-deficient mice. Blood 1998, 92(8):2641-2649.
96. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature 2006, 439(7079):993-997.
2. Nagy A, Gocza E, Diaz EM, Prideaux VR, Ivanyi E, Markkula M, Rossant J: Embryonic stem cells alone are able to support fetal development in the mouse. Development 1990, 110:815-821.
3. Ying QL, Nichols J, Chambers I, Smith A: BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 2003, 115:281-292.
4. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science 1998, 282(5391):1145-1147.
5. Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD: Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci U S A 1998, 95(23):13726-13731.
6. Ying QL, Stavridis M, Griffiths D, Li M, Smith A: Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 2003, 21:183-186.
7. Burt RK, Verda L, Kim DA, Oyama Y, Luo K, Link C: Embryonic stem cells as an alternate marrow donor source: engraftment without graft-versus-host disease. J Exp Med 2004, 199:895-904.
8. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J: Identification of a neural stem cell in the adult mammalian central nervous system. Cell 1999, 96(1):25-34.
9. Chiasson BJ, Tropepe V, Morshead CM, van der Kooy D: Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics. J Neurosci 1999, 19(11):4462-4471.
10. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A: Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999, 97:703-716.
11. Nunes MC, Roy NS, Keyoung HM, Goodman RR, McKhann G, 2nd, Jiang L, Kang J, Nedergaard M, Goldman SA: Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 2003, 9(4):439-447.
12. Morshead CM, van der Kooy D: Disguising adult neural stem cells. Curr Opin Neurobiol 2004, 14(1):125-131.
13. McCulloch EA, Siminovitch L, Till JE: Spleen-Colony Formation in Anemic Mice of Genotype Ww. Science 1964, 144:844-846.
14. Bryder D, Rossi DJ, Weissman IL: Hematopoietic stem cells: the paradigmatic tissue-specific stem cell. Am J Pathol 2006, 169(2):338-346.
15. Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW: AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997, 90(12):5002-5012.
16. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N et al: Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005, 6(3):314-322.
17. Pomerantz J, Blau HM: Nuclear reprogramming: a key to stem cell function in regenerative medicine. Nat Cell Biol 2004, 6(9):810-816.
18. Kawase E, Yamazaki Y, Yagi T, Yanagimachi R, Pedersen RA: Mouse embryonic stem (ES) cell lines established from neuronal cell-derived cloned blastocysts. Genesis 2000, 28(3-4):156-163.
19. Munsie MJ, Michalska AE, O'Brien CM, Trounson AO, Pera MF, Mountford PS: Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol 2000, 10(16):989-992.
20. Wakayama T, Tabar V, Rodriguez I, Perry AC, Studer L, Mombaerts P: Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 2001, 292(5517):740-743.
21. Hochedlinger K, Jaenisch R: Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 2002, 415(6875):1035-1038.
22. Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R: Mice cloned from olfactory sensory neurons. Nature 2004, 428(6978):44-49.
23. Ng RK, Gurdon JB: Epigenetic memory of active gene transcription is inherited through somatic cell nuclear transfer. Proc Natl Acad Sci U S A 2005, 102(6):1957-1962.
24. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ: Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001, 105:369-377.
25. Moore MA: "Turning brain into blood"--clinical applications of stem-cell research in neurobiology and hematology. N Engl J Med 1999,
341(8):605-607.
26. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL: Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 1999, 283(5401):534-537.
27. Brazelton TR, Rossi FM, Keshet GI, Blau HM: From marrow to brain: expression of neuronal phenotypes in adult mice. Science 2000, 290(5497):1775-1779.
28. Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR: Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 2000, 290(5497):1779-1782.
29. Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, Belmonte N, Ferrari G, Leone BE, Bertuzzi F et al: Bone marrow mesenchymal stemcells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood 2005, 106(2):419-427.
30. Jackson KA, Mi T, Goodell MA: Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci U S A 1999, 96(25):14482-14486.
31. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP: Bone marrow as a potential source of hepatic oval cells. Science 1999, 284(5417):1168-1170.
32. Theise ND, Badve S, Saxena R, Henegariu O, Sell S, Crawford JM, Krause DS: Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology 2000, 31(1):235-240.
33. Deng J, Steindler DA, Laywell ED, Petersen BE: Neural trans-differentiation potential of hepatic oval cells in the neonatal mouse brain. Exp Neurol 2003, 182(2):373-382.
34. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M: Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003, 422(6934):897-901.
35. Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS: Lack of a fusion requirement for development of bone marrow-derived epithelia. Science 2004, 305(5680):90-93.
36. Ying QL, Nichols J, Evans EP, Smith AG: Changing potency by spontaneous fusion. Nature 2002, 416(6880):545-548.
37. Wurmser AE, Gage FH: Stem cells: cell fusion causes confusion. Nature 2002, 416(6880):485-487.
38. Teratani T, Yamamoto H, Aoyagi K, Sasaki H, Asari A, Quinn G, Sasaki H, Terada M, Ochiya T: Direct hepatic fate specification from mouse embryonic stem cells. Hepatology 2005, 41(4):836-846.
39. Lian G, Wang C, Teng C, Zhang C, Du L, Zhong Q, Miao C, Ding M, Deng H: Failure of hepatocyte marker-expressing hematopoietic progenitor cells to efficiently convert into hepatocytes in vitro. Exp Hematol 2006, 34(3):348-358.
40. Hansson M, Tonning A, Frandsen U, Petri A, Rajagopal J, Englund MC, Heller RS, Hakansson J, Fleckner J, Skold HN et al: Artifactual insulin release from differentiated embryonic stem cells. Diabetes 2004, 53(10):2603-2609.
41. McKinney-Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA: Muscle-derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci U S A 2002, 99(3):1341-1346.
42. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M et al: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002, 418(6893):41-49.
43. Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ et al: Regulation of neuronal traits by a novel transcriptional complex. Neuron 2001, 31:353-365.
44. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR: A stem cell molecular signature. Science 2002, 298:601-604.
45. Raff M: Adult stem cell plasticity: fact or artifact? Annu Rev Cell Dev Biol 2003, 19:1-22.
46. Wurmser AE, Nakashima K, Summers RG, Toni N, D'Amour KA, Lie DC, Gage FH: Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 2004, 430(6997):350-356.
47. Ianus A, Holz GG, Theise ND, Hussain MA: In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003, 111(6):843-850.
48. Hori Y, Gu X, Xie X, Kim SK: Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2005, 2(4):e103.
49. Oh SH, Muzzonigro TM, Bae SH, LaPlante JM, Hatch HM, Petersen BE: Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest 2004, 84(5):607-617.
50. Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 2004, 53(7):1721-1732.
51. Choi KS, Shin JS, Lee JJ, Kim YS, Kim SB, Kim CW: In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract. Biochem Biophys Res Commun 2005, 330(4):1299-1305.
52. Lechner A, Yang YG, Blacken RA, Wang L, Nolan AL, Habener JF: No evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo. Diabetes 2004, 53(3):616-623.
53. Choi JB, Uchino H, Azuma K, Iwashita N, Tanaka Y, Mochizuki H, Migita M, Shimada T, Kawamori R, Watada H: Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells. Diabetologia 2003, 46(10):1366-1374.
54. Di Gioacchino G, Di Campli C, Zocco MA, Piscaglia AC, Novi M, Santoro M, Santoliquido A, Flore R, Tondi P, Pola P et al: Transdifferentiation of stem cells in pancreatic cells: state of the art. Transplant Proc 2005, 37(6):2662-2663.
55. Tessem JS, DeGregori J: Roles for bone-marrow-derived cells in beta-cell maintenance. Trends Mol Med 2004, 10(11):558-564.
56. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ: SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 2005, 121(7):1109-1121.
57. Shi Y, Hou L, Tang F, Jiang W, Wang P, Ding M, Deng H: Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novelthree-step approach with activin A and all-trans retinoic acid. Stem Cells 2005, 23(5):656-662.
58. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE: Generation of a functional mammary gland from a single stem cell. Nature 2006, 439(7072):84-88.
59. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature 2006, 439(7079):993-997.
60. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D: Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004, 22(9):1115-1124.
61. Morrison SJ, Hemmati HD, Wandycz AM, Weissman IL: The purification and characterization of fetal liver hematopoietic stem cells. Proc Natl Acad Sci U S A 1995, 92(22):10302-10306.
62. Morrison SJ, Weissman IL: The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity 1994, 1(8):661-673.
63. Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL: Identification of a lineage of multipotent hematopoietic progenitors. Development 1997, 124(10):1929-1939.
64. Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF: Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 2001, 412(6848):736-739.
65. Nagato M, Heike T, Kato T, Yamanaka Y, Yoshimoto M, Shimazaki T, Okano H, Nakahata T: Prospective characterization of neural stem cells by flow cytometry analysis using a combination of surface markers. J Neurosci Res 2005, 80(4):456-466.
66. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL: Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 2000, 97(26):14720-14725.
67. Milne HM, Burns CJ, Kitsou-Mylona I, Luther MJ, Minger SL, Persaud SJ, Jones PM: Generation of insulin-expressing cells from mouse embryonic stem cells. Biochem Biophys Res Commun 2005, 328(2):399-403.
68. Keller G: Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 2005, 19(10):1129-1155.
69. Ahlgren U, Jonsson J, Edlund H: The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice. Development 1996, 122(5):1409-1416.
70. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H: beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev 1998, 12(12):1763-1768.
71. Micallef SJ, Janes ME, Knezevic K, Davis RP, Elefanty AG, Stanley EG:Retinoic acid induces Pdx1-positive endoderm in differentiating mouse embryonic stem cells. Diabetes 2005, 54(2):301-305.
72. Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N et al: Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000, 6(5):568-572.
73. Tang DQ, Lu S, Sun YP, Rodrigues E, Chou W, Yang C, Cao LZ, Chang LJ, Yang LJ: Reprogramming liver-stem WB cells into functional insulin-producing cells by persistent expression of Pdx1- and Pdx1-VP16 mediated by lentiviral vectors. Lab Invest 2006, 86(1):83-93.
74. Cao LZ, Tang DQ, Horb ME, Li SW, Yang LJ: High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 2004, 53(12):3168-3178.
75. Lowell S: Stem cells in the genomic age. Genome Biol 2006, 7:315.
76. Van Hoof D, Mummery CL, Heck AJ, Krijgsveld J: Embryonic stem cell proteomics. Expert Rev Proteomics 2006, 3(4):427-437.
77. Bystrykh L, Weersing E, Dontje B, Sutton S, Pletcher MT, Wiltshire T, Su AI, Vellenga E, Wang J, Manly KF et al: Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'. Nat Genet 2005, 37(3):225-232.
78. Shannon MF, Rao S: Transcription. Of chips and ChIPs. Science 2002, 296(5568):666-669.
79. Lee TI, Jenner RG, Boyer LA, Guenther MG, Levine SS, Kumar RM, Chevalier B, Johnstone SE, Cole MF, Isono K et al: Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 2006, 125:301-313.
80. Dvash T, Mayshar Y, Darr H, McElhaney M, Barker D, Yanuka O, Kotkow KJ, Rubin LL, Benvenisty N, Eiges R: Temporal gene expression during differentiation of human embryonic stem cells and embryoid bodies. Hum Reprod 2004, 19(12):2875-2883.
81. Calhoun JD, Rao RR, Warrenfeltz S, Rekaya R, Dalton S, McDonald J, Stice SL: Transcriptional profiling of initial differentiation events in human embryonic stem cells. Biochem Biophys Res Commun 2004, 323(2):453-464.
82. Liu Y, Shin S, Zeng X, Zhan M, Gonzalez R, Mueller FJ, Schwartz CM, Xue H, Li H, Baker SC et al: Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines. BMC Dev Biol 2006, 6:20.
83. Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K et al: Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nat Biotechnol 2004, 22(6):707-716.
84. Boheler KR, Tarasov KV: SAGE analysis to identify embryonic stem cell-predominant transcripts. Methods Mol Biol 2006, 329:195-221.
85. Richards M, Tan SP, Tan JH, Chan WK, Bongso A: The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 2004, 22(1):51-64.
86. Richards M, Tan SP, Chan WK, Bongso A: Reverse serial analysis of gene expression (SAGE) characterization of orphan SAGE tags from human embryonic stem cells identifies the presence of novel transcripts and antisense transcription of key pluripotency genes. Stem Cells 2006, 24(5):1162-1173.
87. Bhattacharya B, Cai J, Luo Y, Miura T, Mejido J, Brimble SN, Zeng X, Schulz TC, Rao MS, Puri RK: Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies. BMC Dev Biol 2005, 5:22.
88. Rao M: Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells. Dev Biol 2004, 275:269-286.
89. Robson P: The maturing of the human embryonic stem cell transcriptome profile. Trends Biotechnol 2004, 22(12):609-612.
90. Gershon D: Microarray technology: an array of opportunities. Nature 2002, 416(6883):885-891.
91. Duret L: Evolution of synonymous codon usage in metazoans. Curr Opin Genet Dev 2002, 12:640-649.
92. Margulies EH, Kardia SL, Innis JW: Identification and prevention of a GC content bias in SAGE libraries. Nucleic Acids Res 2001, 29:E60-60.
93. Matsuzaki Y, Kinjo K, Mulligan RC, Okano H: Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity 2004, 20(1):87-93.
94. Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN et al: Genomic alterations in cultured human embryonic stem cells. Nat Genet 2005, 37(10):1099-1103.
95. Furusawa T, Ikeda M, Inoue F, Ohkoshi K, Hamano T, Tokunaga T: Gene Expression Profiling of Mouse Embryonic Stem Cell Subpopulations. Biol Reprod 2006.
96. Furusawa T, Ohkoshi K, Honda C, Takahashi S, Tokunaga T: Embryonic stem cells expressing both platelet endothelial cell adhesion molecule-1 and stage-specific embryonic antigen-1 differentiate predominantly into epiblast cells in a chimeric embryo. Biol Reprod 2004, 70(5):1452-1457.
97. Kurimoto K, Yabuta Y, Ohinata Y, Ono Y, Uno KD, Yamada RG, Ueda HR, Saitou M: An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis. Nucleic Acids Res 2006, 34(5):e42.
98. Chiang MK, Melton DA: Single-cell transcript analysis of pancreas development. Dev Cell 2003, 4(3):383-393.
99. Kelly DL, Rizzino A: DNA microarray analyses of genes regulated during the differentiation of embryonic stem cells. Mol Reprod Dev 2000, 56(2):113-123.
100. Tanaka TS, Kunath T, Kimber WL, Jaradat SA, Stagg CA, Usuda M, Yokota T, Niwa H, Rossant J, Ko MS: Gene expression profiling of embryo-derived stem cells reveals candidate genes associated with pluripotency and lineage specificity. Genome Res 2002, 12(12):1921-1928.
101. Sperger JM, Chen X, Draper JS, Antosiewicz JE, Chon CH, Jones SB, Brooks JD, Andrews PW, Brown PO, Thomson JA: Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci U S A 2003, 100(23):13350-13355.
102. Palmqvist L, Glover CH, Hsu L, Lu M, Bossen B, Piret JM, Humphries RK, Helgason CD: Correlation of murine embryonic stem cell gene expression profiles with functional measures of pluripotency. Stem Cells 2005, 23(5):663-680.
103. Beqqali A, Kloots J, Ward-van Oostwaard D, Mummery C, Passier R: Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells 2006, 24(8):1956-1967.
104. Pritsker M, Ford NR, Jenq HT, Lemischka IR: Genomewide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells. Proc Natl Acad Sci U S A 2006, 103(18):6946-6951.
105. Park IK, He Y, Lin F, Laerum OD, Tian Q, Bumgarner R, Klug CA, Li K, Kuhr C, Doyle MJ et al: Differential gene expression profiling of adult murine hematopoietic stem cells. Blood 2002, 99(2):488-498.
106. Terskikh AV, Miyamoto T, Chang C, Diatchenko L, Weissman IL: Gene expression analysis of purified hematopoietic stem cells and committed progenitors. Blood 2003, 102(1):94-101.
107. Georgantas RW, 3rd, Tanadve V, Malehorn M, Heimfeld S, Chen C, Carr L, Martinez-Murillo F, Riggins G, Kowalski J, Civin CI: Microarray and serial analysis of gene expression analyses identify known and novel transcripts overexpressed in hematopoietic stem cells. Cancer Res 2004, 64(13):4434-4441.
108. Eckfeldt CE, Mendenhall EM, Flynn CM, Wang TF, Pickart MA, Grindle SM, Ekker SC, Verfaillie CM: Functional analysis of human hematopoietic stem cell gene expression using zebrafish. PLoS Biol 2005, 3(8):e254.
109. Huttmann A, Duhrsen U, Heydarian K, Klein-Hitpass L, Boes T, Boyd AW, Li CL: Gene expression profiles in murine hematopoietic stem cells revisited: analysis of cDNA libraries reveals high levels of translational and metabolic activities. Stem Cells 2006, 24(7):1719-1727.
110. Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL: From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci U S A 2001, 98(14):7934-7939.
111. Easterday MC, Dougherty JD, Jackson RL, Ou J, Nakano I, Paucar AA, Roobini B, Dianati M, Irvin DK, Weissman IL et al: Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations. Dev Biol 2003, 264(2):309-322.
112. Kim CG, Lee JJ, Jung DY, Jeon J, Heo HS, Kang HC, Shin JH, Cho YS, Cha KJ, Kim CG et al: Profiling of differentially expressed genes in human stem cells by cDNA microarray. Mol Cells 2006, 21(3):343-355.
113. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA: "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 2002, 298:597-600.
114. Fortunel NO, Otu HH, Ng HH, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA et al: Comment on " 'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science 2003, 302(5644):393; author reply 393.
115. Evsikov AV, Solter D: Comment on " 'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science 2003, 302(5644):393; author reply 393.
116. Vogel G: Stem cell research. Same results, different interpretations. Science 2003, 299(5605):324.
117. Giudice G: Conserved cellular and molecular mechanisms in development. Cell Biol Int 2001, 25(11):1081-1090.
118. Sato N, Sanjuan IM, Heke M, Uchida M, Naef F, Brivanlou AH: Molecular signature of human embryonic stem cells and its comparison with the mouse. Dev Biol 2003, 260(2):404-413.
119. Cotsarelis G: Gene expression profiling gets to the root of human hair follicle stem cells. J Clin Invest 2006, 116(1):19-22.
120. Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB, Brady JN, Udey MC, Vogel JC: Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 2006, 116(1):249-260.
121. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E: Defining the epithelial stem cell niche in skin. Science 2004, 303(5656):359-363.
122. Christiano AM: Epithelial stem cells: stepping out of their niche. Cell 2004, 118(5):530-532.
123. Mitalipov S, Kuo HC, Byrne J, Clepper L, Meisner L, Johnson J, Zeier R, Wolf D: Isolation and Characterization of Novel Rhesus Monkey Embryonic Stem Cell Lines. Stem Cells 2006.
124. Byrne JA, Mitalipov SM, Clepper L, Wolf DP: Transcriptional Profiling of Rhesus Monkey Embryonic Stem Cells. Biol Reprod 2006.
125. Roloff TC, Nuber UA: Chromatin, epigenetics and stem cells. Eur J Cell Biol 2005, 84(2-3):123-135.
126. Peterson CL, Laniel MA: Histones and histone modifications. Curr Biol 2004, 14(14):R546-551.
127. Margueron R, Trojer P, Reinberg D: The key to development: interpreting the histone code? Curr Opin Genet Dev 2005, 15(2):163-176.
128. Jenuwein T, Allis CD: Translating the histone code. Science 2001, 293(5532):1074-1080.
129. Kubicek S, Schotta G, Lachner M, Sengupta R, Kohlmaier A, Perez-Burgos L, Linderson Y, Martens JH, O'Sullivan RJ, Fodor BD et al: The role of histone modifications in epigenetic transitions during normal and perturbed development. Ernst Schering Res Found Workshop 2006(57):1-27.
130. Santos-Rosa H, Caldas C: Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 2005, 41(16):2381-2402.
131. de la Serna IL, Ohkawa Y, Imbalzano AN: Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nat Rev Genet 2006, 7(6):461-473.
132. Song MR, Ghosh A: FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat Neurosci 2004, 7:229-235.
133. Ajamian F, Suuronen T, Salminen A, Reeben M: Upregulation of class II histone deacetylases mRNA during neural differentiation of cultured rat hippocampal progenitor cells. Neurosci Lett 2003, 346:57-60.
134. Rasmussen TP: Embryonic stem cell differentiation: a chromatin perspective. Reprod Biol Endocrinol 2003, 1:100.
135. Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM, Gouti M, Casanova M, Warnes G, Merkenschlager M et al: Chromatin signatures of pluripotent cell lines. Nat Cell Biol 2006, 8(5):532-538.
136. Szutorisz H, Canzonetta C, Georgiou A, Chow CM, Tora L, Dillon N: Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol Cell Biol 2005, 25(5):1804-1820.
137. Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK et al: Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006, 441(7091):349-353.
138. Orkin SH: Chipping away at the embryonic stem cell network. Cell 2005, 122(6):828-830.
139. Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J et al: The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 2006, 38(4):431-440.
140. Buszczak M, Spradling AC: Searching chromatin for stem cell identity. Cell 2006, 125(2):233-236.
141. Squazzo SL, O'Geen H, Komashko VM, Krig SR, Jin VX, Jang SW, Margueron R, Reinberg D, Green R, Farnham PJ: Suz12 binds to silenced regions of the genome in a cell-type-specific manner. Genome Res 2006, 16(7):890-900.
142. Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K et al: A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 2006, 125(2):315-326.
143. Kaji K, Caballero IM, MacLeod R, Nichols J, Wilson VA, Hendrich B: The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 2006, 8(3):285-292.
144. Wang X, Ge S, Gonzalez I, McNamara G, Rountree CB, Xi KK, Huang G, Bhushan A, Crooks GM: Formation of pancreatic duct epithelium from bone marrow during neonatal development. Stem Cells 2006, 24(2):307-314.
145. Bibikova M, Chudin E, Wu B, Zhou L, Garcia EW, Liu Y, Shin S, Plaia TW, Auerbach JM, Arking DE et al: Human embryonic stem cells have a unique epigenetic signature. Genome Res 2006, 16(9):1075-1083.
146. Okusaka T, Matsumura Y, Aoki K: New approaches for pancreatic cancer in Japan. Cancer Chemother Pharmacol 2004, 54 Suppl 1:S78-82.
147. Shen Y, Chow J, Wang Z, Fan G: Abnormal CpG island methylation occurs during in vitro differentiation of human embryonic stem cells. Hum Mol Genet 2006, 15(17):2623-2635.
148. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF: Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 2003, 423(6937):302-305.
149. Lessard J, Sauvageau G: Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003, 423(6937):255-260.
150. Akala OO, Clarke MF: Hematopoietic stem cell self-renewal. Curr Opin Genet Dev 2006.
151. Kunisato A, Chiba S, Nakagami-Yamaguchi E, Kumano K, Saito T, Masuda S, Yamaguchi T, Osawa M, Kageyama R, Nakauchi H et al: HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo. Blood 2003, 101(5):1777-1783.
152. Iwama A, Oguro H, Negishi M, Kato Y, Nakauchia H: Epigenetic regulation of hematopoietic stem cell self-renewal by polycomb group genes. Int J Hematol 2005, 81(4):294-300.
153. Cao R, Tsukada Y, Zhang Y: Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 2005, 20(6):845-854.
154. Kamminga LM, Bystrykh LV, de Boer A, Houwer S, Douma J, Weersing E, Dontje B, de Haan G: The Polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 2006, 107(5):2170-2179.
155. Nemeth MJ, Kirby MR, Bodine DM: Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and differentiation. Proc Natl Acad Sci U S A 2006.
156. Georgopoulos K: Haematopoietic cell-fate decisions, chromatin regulation and ikaros. Nat Rev Immunol 2002, 2(3):162-174.
157. Lopez RA, Schoetz S, DeAngelis K, O'Neill D, Bank A: Multiple hematopoietic defects and delayed globin switching in Ikaros null mice. Proc Natl Acad Sci U S A 2002, 99(2):602-607.
158. Cobb BS, Smale ST: Ikaros-family proteins: in search of molecular functions during lymphocyte development. Curr Top Microbiol Immunol2005, 290:29-47.
159. Kondo T: Epigenetic alchemy for cell fate conversion. Curr Opin Genet Dev 2006, 16(5):502-507.
160. Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G et al: Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 2002, 298(5599):1747-1752.
161. Lunyak VV, Rosenfeld MG: No rest for REST: REST/NRSF regulation of neurogenesis. Cell 2005, 121(4):499-501.
162. Su X, Gopalakrishnan V, Stearns D, Aldape K, Lang FF, Fuller G, Snyder E, Eberhart CG, Majumder S: Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Mol Cell Biol 2006, 26(5):1666-1678.
163. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH: A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 2004, 116(6):779-793.
164. Fleitz J, Rumelhart S, Goldman F, Ambruso D, Sokol RJ, Pacini D, Quinones R, Holida M, Lee N, Tannous R et al: Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond syndrome. Bone Marrow Transplant 2002, 29(1):75-79.
165. Matsumoto S, Banine F, Struve J, Xing R, Adams C, Liu Y, Metzger D, Chambon P, Rao MS, Sherman LS: Brg1 is required for murine neural stem cell maintenance and gliogenesis. Dev Biol 2006, 289(2):372-383.
166. Schmittwolf C, Kirchhof N, Jauch A, Durr M, Harder F, Zenke M, Muller AM: In vivo haematopoietic activity is induced in neurosphere cells by chromatin-modifying agents. Embo J 2005, 24(3):554-566.
167. Araki H, Mahmud N, Milhem M, Nunez R, Xu M, Beam CA, Hoffman R: Expansion of human umbilical cord blood SCID-repopulating cells using chromatin-modifying agents. Exp Hematol 2006, 34(2):140-149.
168. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
169. Bernardi G: Isochores and the evolutionary genomics of vertebrates. Gene 2000, 241:3-17.
170. Kosak ST, Groudine M: Gene order and dynamic domains. Science 2004, 306(5696):644-647.
171. Kosak ST, Groudine M: Form follows function: The genomic organization of cellular differentiation. Genes Dev 2004, 18:1371-1384.
172. Vinogradov AE: Noncoding DNA, isochores and gene expression: nucleosome formation potential. Nucleic Acids Res 2005, 33:559-563.
173. Vinogradov AE: DNA helix: the importance of being GC-rich. Nucleic Acids Res 2003, 31:1838-1844.
174. Hiratani I, Leskovar A, Gilbert DM: Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A 2004,101:16861-16866.
175. Zhou J, Liu WJ, Peng SW, Sun XY, Frazer I: Papillomavirus capsid protein expression level depends on the match between codon usage and tRNA availability. J Virol 1999, 73:4972-4982.
176. Kudla G, Lipinski L, Caffin F, Helwak A, Zylicz M: High guanine and cytosine content increases mRNA levels in mammalian cells. PLoS Biol 2006, 4:e180.
177. Li H, Liu Y, Shin S, Sun Y, Loring JF, Mattson MP, Rao MS, Zhan M: Transcriptome coexpression map of human embryonic stem cells. BMC Genomics 2006, 7:103.
178. Gilbert SF: The morphogenesis of evolutionary developmental biology. Int J Dev Biol 2003, 47:467-477.
179. Arthur W: The emerging conceptual framework of evolutionary developmental biology. Nature 2002, 415:757-764.
180. Hall BK: Evo-Devo: evolutionary developmental mechanisms. Int J Dev Biol 2003, 47(7-8):491-495.
181. Garcia-Fernandez J: The genesis and evolution of homeobox gene clusters. Nat Rev Genet 2005, 6(12):881-892.
182. Chang CC, Cook CE: Trends in genomic 'evo-devo'. Genome Biol 2002, 3:REPORTS4019.
183. Ponger L, Duret L, Mouchiroud D: Determinants of CpG islands: expression in early embryo and isochore structure. Genome Res 2001, 11:1854-1860.
184. Castillo-Davis CI, Hartl DL: Genome evolution and developmental constraint in Caenorhabditis elegans. Mol Biol Evol 2002, 19:728-735.
185. Gothert JR, Gustin SE, Hall MA, Green AR, Gottgens B, Izon DJ, Begley CG: In vivo fate-tracing studies using the Scl stem cell enhancer: embryonic hematopoietic stem cells significantly contribute to adult hematopoiesis. Blood 2005, 105:2724-2732.
1. Duret L: Evolution of synonymous codon usage in metazoans. Curr Opin Genet Dev 2002, 12:640-649.
2. Gouy M, Gautier C: Codon usage in bacteria: correlation with gene expressivity. Nucleic Acids Res 1982, 10:7055-7074.
3. Sharp PM, Li WH: An evolutionary perspective on synonymous codon usage in unicellular organisms. J Mol Evol 1986, 24:28-38.
4. Sharp PM, Tuohy TM, Mosurski KR: Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res 1986, 14:5125-5143.
5. Coghlan A, Wolfe KH: Relationship of codon bias to mRNA concentration and protein length in Saccharomyces cerevisiae. Yeast 2000, 16:1131-1145.
6. Akashi H: Gene expression and molecular evolution. Curr Opin Genet Dev 2001, 11:660-666.
7. Stenico M, Lloyd AT, Sharp PM: Codon usage in Caenorhabditis elegans: delineation of translational selection and mutational biases. Nucleic Acids Res 1994, 22:2437-2446.
8. Moriyama EN, Powell JR: Codon usage bias and tRNA abundance in Drosophila. J Mol Evol 1997, 45:514-523.
9. Powell JR, Moriyama EN: Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A 1997, 94:7784-7790.
10. Duret L, Mouchiroud D: Expression pattern and, surprisingly, gene length shape codon usage in Caenorhabditis, Drosophila, and Arabidopsis. Proc Natl Acad Sci U S A 1999, 96:4482-4487.
11. Dong H, Nilsson L, Kurland CG: Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J Mol Biol 1996, 260:649-663.
12. Akashi H, Eyre-Walker A: Translational selection and molecular evolution. Curr Opin Genet Dev 1998, 8:688-693.
13. Kanaya S, Yamada Y, Kinouchi M, Kudo Y, Ikemura T: Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessed by multivariate analysis. J Mol Evol 2001, 53:290-298.
14. Duret L: tRNA gene number and codon usage in the C. elegans genome are co-adapted for optimal translation of highly expressed genes. Trends Genet 2000, 16:287-289.
15. Bulmer M: The selection-mutation-drift theory of synonymous codon usage. Genetics 1991, 129:897-907.
16. Semon M, Mouchiroud D, Duret L: Relationship between gene expression and GC-content in mammals: statistical significance and biological relevance. Hum Mol Genet 2005, 14:421-427.
17. Konu O, Li MD: Correlations between mRNA expression levels and GC contents of coding and untranslated regions of genes in rodents. J MolEvol 2002, 54:35-41.
18. Vinogradov AE: Isochores and tissue-specificity. Nucleic Acids Res 2003, 31:5212-5220.
19. Urrutia AO, Hurst LD: The signature of selection mediated by expression on human genes. Genome Res 2003, 13:2260-2264.
20. Comeron JM: Selective and mutational patterns associated with gene expression in humans: influences on synonymous composition and intron presence. Genetics 2004, 167:1293-1304.
21. Margulies EH, Kardia SL, Innis JW: Identification and prevention of a GC content bias in SAGE libraries. Nucleic Acids Res 2001, 29:E60-60.
22. DeBry RW, Marzluff WF: Selection on silent sites in the rodent H3 histone gene family. Genetics 1994, 138:191-202.
23. Mouchiroud D, Fichant G, Bernardi G: Compositional compartmentalization and gene composition in the genome of vertebrates. J Mol Evol 1987, 26:198-204.
24. Bernardi G: The isochore organization of the human genome and its evolutionary history--a review. Gene 1993, 135:57-66.
25. Bernardi G: The human genome: organization and evolutionary history. Annu Rev Genet 1995, 29:445-476.
26. Pesole G, Bernardi G, Saccone C: Isochore specificity of AUG initiator context of human genes. FEBS Lett 1999, 464:60-62.
27. Lercher MJ, Urrutia AO, Pavlicek A, Hurst LD: A unification of mosaic structures in the human genome. Hum Mol Genet 2003, 12:2411-2415.
28. Ponger L, Duret L, Mouchiroud D: Determinants of CpG islands: expression in early embryo and isochore structure. Genome Res 2001, 11:1854-1860.
29. Goncalves I, Duret L, Mouchiroud D: Nature and structure of human genes that generate retropseudogenes. Genome Res 2000, 10:672-678.
30. D'Onofrio G: Expression patterns and gene distribution in the human genome. Gene 2002, 300:155-160.
31. Zhang L, Li WH: Mammalian housekeeping genes evolve more slowly than tissue-specific genes. Mol Biol Evol 2004, 21:236-239.
32. Plotkin JB, Robins H, Levine AJ: Tissue-specific codon usage and the expression of human genes. Proc Natl Acad Sci U S A 2004, 101:12588-12591.
33. Semon M, Lobry JR, Duret L: No evidence for tissue-specific adaptation of synonymous codon usage in humans. Mol Biol Evol 2006, 23:523-529.
34. Wolfe KH, Sharp PM, Li WH: Mutation rates differ among regions of the mammalian genome. Nature 1989, 337:283-285.
35. Eyre-Walker AC: An analysis of codon usage in mammals: selection or mutation bias? J Mol Evol 1991, 33:442-449.
36. Sharp PM, Averof M, Lloyd AT, Matassi G, Peden JF: DNA sequence evolution: the sounds of silence. Philos Trans R Soc Lond B Biol Sci 1995, 349:241-247.
37. Hughes AL, Yeager M: Comparative evolutionary rates of introns and exons in murine rodents. J Mol Evol 1997, 45:125-130.
38. Francino MP, Ochman H: Isochores result from mutation not selection. Nature 1999, 400:30-31.
39. Castillo-Davis CI, Mekhedov SL, Hartl DL, Koonin EV, Kondrashov FA: Selection for short introns in highly expressed genes. Nat Genet 2002, 31:415-418.
40. Eyre-Walker A: Evidence of selection on silent site base composition in mammals: potential implications for the evolution of isochores and junk DNA. Genetics 1999, 152:675-683.
41. Hurst LD, Pal C: Evidence for purifying selection acting on silent sites in BRCA1. Trends Genet 2001, 17:62-65.
42. Hellmann I, Zollner S, Enard W, Ebersberger I, Nickel B, Paabo S: Selection on human genes as revealed by comparisons to chimpanzee cDNA. Genome Res 2003, 13:831-837.
43. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21:1014-1023.
44. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21(6):1014-1023.
45. Schattner P, Diekhans M: Regions of extreme synonymous codon selection in mammalian genes. Nucleic Acids Res 2006, 34:1700-1710.
46. Chamary JV, Parmley JL, Hurst LD: Hearing silence: non-neutral evolution at synonymous sites in mammals. Nat Rev Genet 2006, 7:98-108.
47. Vinogradov AE: Noncoding DNA, isochores and gene expression: nucleosome formation potential. Nucleic Acids Res 2005, 33:559-563.
48. Vinogradov AE: DNA helix: the importance of being GC-rich. Nucleic Acids Res 2003, 31:1838-1844.
49. Parmley JL, Chamary JV, Hurst LD: Evidence for purifying selection against synonymous mutations in mammalian exonic splicing enhancers. Mol Biol Evol 2006, 23:301-309.
50. Willie E, Majewski J: Evidence for codon bias selection at the pre-mRNA level in eukaryotes. Trends Genet 2004, 20:534-538.
51. Chamary JV, Hurst LD: Evidence for selection on synonymous mutations affecting stability of mRNA secondary structure in mammals. Genome Biol 2005, 6:R75.
52. Lavner Y, Kotlar D: Codon bias as a factor in regulating expression via translation rate in the human genome. Gene 2005, 345:127-138.
53. Comeron JM: Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans. Proc Natl Acad Sci U S A 2006, 103:6940-6945.
54. Oresic M, Dehn M, Korenblum D, Shalloway D: Tracing specific synonymous codon-secondary structure correlations through evolution. JMol Evol 2003, 56:473-484.
55. Archetti M: Selection on codon usage for error minimization at the protein level. J Mol Evol 2004, 59:400-415.
56. Musto H, Cruveiller S, D'Onofrio G, Romero H, Bernardi G: Translational selection on codon usage in Xenopus laevis. Mol Biol Evol 2001, 18:1703-1707.
57. Romero H, Zavala A, Musto H, Bernardi G: The influence of translational selection on codon usage in fishes from the family Cyprinidae. Gene 2003, 317:141-147.
58. Fryxell KJ, Zuckerkandl E: Cytosine deamination plays a primary role in the evolution of mammalian isochores. Mol Biol Evol 2000, 17:1371-1383.
59. Francino MP, Ochman H: Deamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences. Mol Biol Evol 2001, 18:1147-1150.
60. Green P, Ewing B, Miller W, Thomas PJ, Green ED: Transcription-associated mutational asymmetry in mammalian evolution. Nat Genet 2003, 33:514-517.
61. Iida K, Akashi H: A test of translational selection at 'silent' sites in the human genome: base composition comparisons in alternatively spliced genes. Gene 2000, 261:93-105.
62. Smith NG, Hurst LD: The effect of tandem substitutions on the correlation between synonymous and nonsynonymous rates in rodents. Genetics 1999, 153:1395-1402.
63. Bielawski JP, Dunn KA, Yang Z: Rates of nucleotide substitution and mammalian nuclear gene evolution. Approximate and maximum-likelihood methods lead to different conclusions. Genetics 2000, 156:1299-1308.
64. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
65. Chen FC, Wang SS, Chen CJ, Li WH, Chuang TJ: Alternatively and Constitutively Spliced Exons Are Subject to Different Evolutionary Forces. Mol Biol Evol 2006, 23:675-682.
66. Fullerton SM, Bernardo Carvalho A, Clark AG: Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 2001, 18:1139-1142.
67. Galtier N, Piganeau G, Mouchiroud D, Duret L: GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 2001, 159:907-911.
68. Galtier N: Gene conversion drives GC content evolution in mammalian histones. Trends Genet 2003, 19:65-68.
69. Meunier J, Duret L: Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 2004, 21:984-990.
70. Montoya-Burgos JI, Boursot P, Galtier N: Recombination explains isochores in mammalian genomes. Trends Genet 2003, 19:128-130.
71. Nickoloff JA: Transcription enhances intrachromosomal homologous recombination in mammalian cells. Mol Cell Biol 1992, 12:5311-5318.
72. Droge P: Transcription-driven site-specific DNA recombination in vitro. Proc Natl Acad Sci U S A 1993, 90:2759-2763.
73. Nicolas A: Relationship between transcription and initiation of meiotic recombination: toward chromatin accessibility. Proc Natl Acad Sci U S A 1998, 95:87-89.
74. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA: "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 2002, 298:597-600.
75. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR: A stem cell molecular signature. Science 2002, 298:601-604.
76. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A et al: Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A 2002, 99:4465-4470.
77. Sharp PM, Tuohy TM, Mosurski KR: Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes. Nucleic Acids Res 1986, 14(13):5125-5143.
78. Duret L, Mouchiroud D: Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol Biol Evol 2000, 17:68-74.
79. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al: Initial sequencing and analysis of the human genome. Nature 2001, 409(6822):860-921.
80. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P et al: Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420(6915):520-562.
81. Agris PF: Decoding the genome: a modified view. Nucleic Acids Res 2004, 32:223-238.
82. Murphy FVt, Ramakrishnan V, Malkiewicz A, Agris PF: The role of modifications in codon discrimination by tRNA(Lys)UUU. Nat Struct Mol Biol 2004, 11:1186-1191.
83. Tong KL, Wong JT: Anticodon and wobble evolution. Gene 2004, 333:169-177.
84. Umeda N, Suzuki T, Yukawa M, Ohya Y, Shindo H, Watanabe K: Mitochondria-specific RNA-modifying enzymes responsible for the biosynthesis of the wobble base in mitochondrial tRNAs. Implications for the molecular pathogenesis of human mitochondrial diseases. J Biol Chem 2005, 280:1613-1624.
85. Ikemura T: Codon usage and tRNA content in unicellular and multicellular organisms. Mol Biol Evol 1985, 2:13-34.
86. White BN, Tener GM, Holden J, Suzuki DT: Analysis of tRNAs during the development of Drosophila. Dev Biol 1973, 33:185-195.
87. Hosbach HA, Kubli E: Transfer RNA in aging Drosophila: II. Isoacceptor patterns. Mech Ageing Dev 1979, 10:141-149.
88. Beutler E, Gelbart T, Han JH, Koziol JA, Beutler B: Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage. Proc Natl Acad Sci U S A 1989, 86(1):192-196.
89. Karlin S, Mrazek J: What drives codon choices in human genes? J Mol Biol 1996, 262(4):459-472.
90. Stryer L: Biochemistry, 4 edn. USA; 1995.
91. Rinkevich B: A critical approach to the definition of Darwinian units of selection. Biol Bull 2000, 199(3):231-240.
92. Weissman IL: Stem cells: units of development, units of regeneration, and units in evolution. Cell 2000, 100:157-168.
93. Stoner DS, Rinkevich B, Weissman IL: Heritable germ and somatic cell lineage competitions in chimeric colonial protochordates. Proc Natl Acad Sci U S A 1999, 96(16):9148-9153.
94. Laird DJ, De Tomaso AW, Weissman IL: Stem cells are units of natural selection in a colonial ascidian. Cell 2005, 123:1351-1360.
95. Rinkevich B: The colonial urochordate Botryllus schlosseri: from stem cells and natural tissue transplantation to issues in evolutionary ecology. Bioessays 2002, 24(8):730-740.
96. Mayr WR, Pausch V, Schnedl W: Human chimaera detectable only by investigation of her progeny. Nature 1979, 277(5693):210-211.
97. Calabrese P, Tavare S, Shibata D: Pretumor progression: clonal evolution of human stem cell populations. Am J Pathol 2004, 164(4):1337-1346.
98. Clarke MF, Fuller M: Stem cells and cancer: two faces of eve. Cell 2006, 124:1111-1115.
99. Huntly BJ, Gilliland DG: Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 2005, 5:311-321.
1. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
2. Bernardi G: Isochores and the evolutionary genomics of vertebrates. Gene 2000, 241:3-17.
3. Bernardi G, Olofsson B, Filipski J, Zerial M, Salinas J, Cuny G, Meunier-Rotival M, Rodier F: The mosaic genome of warm-blooded vertebrates. Science 1985, 228:953-958.
4. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W et al: Initial sequencing and analysis of the human genome. Nature 2001, 409(6822):860-921.
5. Hurst LD, Pal C, Lercher MJ: The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet 2004, 5(4):299-310.
6. Clay O, Carels N, Douady C, Macaya G, Bernardi G: Compositional heterogeneity within and among isochores in mammalian genomes. I. CsCl and sequence analyses. Gene 2001, 276(1-2):15-24.
7. Macaya G, Thiery JP, Bernardi G: An approach to the organization of eukaryotic genomes at a macromolecular level. J Mol Biol 1976, 108(1):237-254.
8. Haring D, Kypr J: No isochores in the human chromosomes 21 and 22? Biochem Biophys Res Commun 2001, 280(2):567-573.
9. Clay O, Bernardi G: The isochores in human chromosomes 21 and 22. Biochem Biophys Res Commun 2001, 285(4):855-856.
10. Bernardi G: Misunderstandings about isochores. Part 1. Gene 2001, 276(1-2):3-13.
11. Pavlicek A, Clay O, Jabbari K, Paces J, Bernardi G: Isochore conservation between MHC regions on human chromosome 6 and mouse chromosome
17. FEBS Lett 2002, 511(1-3):175-177.
12. Li W: Are isochore sequences homogeneous? Gene 2002, 300(1-2):129-139.
13. Li W, Bernaola-Galvan P, Carpena P, Oliver JL: Isochores merit the prefix 'iso'. Comput Biol Chem 2003, 27(1):5-10.
14. Li W: Delineating relative homogeneous G+C domains in DNA sequences. Gene 2001, 276(1-2):57-72.
15. Cohen N, Dagan T, Stone L, Graur D: GC composition of the human genome: in search of isochores. Mol Biol Evol 2005, 22(5):1260-1272.
16. Clay O, Bernardi G: How not to search for isochores: a reply to Cohen et Al. Mol Biol Evol 2005, 22(12):2315-2317.
17. Finishing the euchromatic sequence of the human genome. Nature 2004, 431(7011):931-945.
18. Costantini M, Clay O, Auletta F, Bernardi G: An isochore map of human chromosomes. Genome Res 2006, 16(4):536-541.
19. Zhang CT, Wang J, Zhang R: A novel method to calculate the G+C content of genomic DNA sequences. J Biomol Struct Dyn 2001, 19(2):333-341.
20. Zhang CT, Zhang R: Analysis of distribution of bases in the coding sequences by a diagrammatic technique. Nucleic Acids Res 1991, 19(22):6313-6317.
21. Zhang R, Zhang CT: Z curves, an intutive tool for visualizing and analyzing the DNA sequences. J Biomol Struct Dyn 1994, 11(4):767-782.
22. Zhang CT, Zhang R: An isochore map of the human genome based on the Z curve method. Gene 2003, 317(1-2):127-135.
23. Zhang CT, Zhang R: Isochore structures in the mouse genome. Genomics 2004, 83(3):384-394.
24. Gao F, Zhang CT: Isochore structures in the chicken genome. Febs J 2006, 273(8):1637-1648.
25. Zhang R, Zhang CT: Isochore structures in the genome of the plant Arabidopsis thaliana. J Mol Evol 2004, 59(2):227-238.
26. Gao F, Zhang CT: GC-Profile: a web-based tool for visualizing and analyzing the variation of GC content in genomic sequences. Nucleic Acids Res 2006, 34(Web Server issue):W686-691.
27. Fryxell KJ, Zuckerkandl E: Cytosine deamination plays a primary role in the evolution of mammalian isochores. Mol Biol Evol 2000, 17:1371-1383.
28. Francino MP, Ochman H: Deamination as the basis of strand-asymmetric evolution in transcribed Escherichia coli sequences. Mol Biol Evol 2001, 18:1147-1150.
29. Green P, Ewing B, Miller W, Thomas PJ, Green ED: Transcription-associated mutational asymmetry in mammalian evolution. Nat Genet 2003, 33:514-517.
30. Wolfe KH, Sharp PM, Li WH: Mutation rates differ among regions of the mammalian genome. Nature 1989, 337:283-285.
31. Francino MP, Ochman H: Isochores result from mutation not selection. Nature 1999, 400:30-31.
32. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21(6):1014-1023.
33. Alvarez-Valin F, Lamolle G, Bernardi G: Isochores, GC3 and mutation biases in the human genome. Gene 2002, 300(1-2):161-168.
34. Belle EM, Smith N, Eyre-Walker A: Analysis of the phylogenetic distribution of isochores in vertebrates and a test of the thermal stability hypothesis. J Mol Evol 2002, 55(3):356-363.
35. Hughes S, Zelus D, Mouchiroud D: Warm-blooded isochore structure in Nile crocodile and turtle. Mol Biol Evol 1999, 16(11):1521-1527.
36. Hurst LD, Merchant AR: High guanine-cytosine content is not an adaptation to high temperature: a comparative analysis amongst prokaryotes. Proc Biol Sci 2001, 268(1466):493-497.
37. Galtier N, Lobry JR: Relationships between genomic G+C content, RNA secondary structures, and optimal growth temperature in prokaryotes. J Mol Evol 1997, 44(6):632-636.
38. Jabbari K, Bernardi G: Body temperature and evolutionary genomics of vertebrates: a lesson from the genomes of Takifugu rubripes and Tetraodon nigroviridis. Gene 2004, 333:179-181.
39. Musto H, Naya H, Zavala A, Romero H, Alvarez-Valin F, Bernardi G: Genomic GC level, optimal growth temperature, and genome size in prokaryotes. Biochem Biophys Res Commun 2006, 347(1):1-3.
40. Galtier N, Piganeau G, Mouchiroud D, Duret L: GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 2001, 159:907-911.
41. Meunier J, Duret L: Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 2004, 21:984-990.
42. Montoya-Burgos JI, Boursot P, Galtier N: Recombination explains isochores in mammalian genomes. Trends Genet 2003, 19:128-130.
43. Galtier N: Gene conversion drives GC content evolution in mammalian histones. Trends Genet 2003, 19:65-68.
44. Fullerton SM, Bernardo Carvalho A, Clark AG: Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 2001, 18:1139-1142.
45. Belle EM, Duret L, Galtier N, Eyre-Walker A: The decline of isochores in mammals: an assessment of the GC content variation along the mammalian phylogeny. J Mol Evol 2004, 58(6):653-660.
46. Duret L, Semon M, Piganeau G, Mouchiroud D, Galtier N: Vanishing GC-rich isochores in mammalian genomes. Genetics 2002, 162(4):1837-1847.
47. Webster MT, Axelsson E, Ellegren H: Strong regional biases in nucleotide substitution in the chicken genome. Mol Biol Evol 2006, 23(6):1203-1216.
48. Arndt PF, Petrov DA, Hwa T: Distinct changes of genomic biases in nucleotide substitution at the time of Mammalian radiation. Mol Biol Evol 2003, 20(11):1887-1896.
49. Lercher MJ, Smith NG, Eyre-Walker A, Hurst LD: The evolution of isochores: evidence from SNP frequency distributions. Genetics 2002, 162(4):1805-1810.
50. Alvarez-Valin F, Clay O, Cruveiller S, Bernardi G: Inaccurate reconstruction of ancestral GC levels creates a "vanishing isochores" effect. Mol Phylogenet Evol 2004, 31(2):788-793.
51. Hackenberg M, Bernaola-Galvan P, Carpena P, Oliver JL: The biased distribution of Alus in human isochores might be driven by recombination. J Mol Evol 2005, 60(3):365-377.
52. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P et al: Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420(6915):520-562.
53. Kruglyak S, Tang H: Regulation of adjacent yeast genes. Trends Genet 2000, 16(3):109-111.
54. Lercher MJ, Urrutia AO, Hurst LD: Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 2002, 31(2):180-183.
55. Birnbaum K, Shasha DE, Wang JY, Jung JW, Lambert GM, Galbraith DW, Benfey PN: A gene expression map of the Arabidopsis root. Science 2003, 302(5652):1956-1960.
56. Spellman PT, Rubin GM: Evidence for large domains of similarly expressed genes in the Drosophila genome. J Biol 2002, 1(1):5.
57. Boutanaev AM, Kalmykova AI, Shevelyov YY, Nurminsky DI: Large clusters of co-expressed genes in the Drosophila genome. Nature 2002, 420(6916):666-669.
58. Parisi M, Nuttall R, Edwards P, Minor J, Naiman D, Lu J, Doctolero M, Vainer M, Chan C, Malley J et al: A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults. Genome Biol 2004, 5(6):R40.
59. Stolc V, Gauhar Z, Mason C, Halasz G, van Batenburg MF, Rifkin SA, Hua S, Herreman T, Tongprasit W, Barbano PE et al: A gene expression map for the euchromatic genome of Drosophila melanogaster. Science 2004, 306(5696):655-660.
60. Garcia-Fernandez J: The genesis and evolution of homeobox gene clusters. Nat Rev Genet 2005, 6(12):881-892.
61. Ko MS, Threat TA, Wang X, Horton JH, Cui Y, Wang X, Pryor E, Paris J, Wells-Smith J, Kitchen JR et al: Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome. Hum Mol Genet 1998, 7(12):1967-1978.
62. Reymond A, Marigo V, Yaylaoglu MB, Leoni A, Ucla C, Scamuffa N, Caccioppoli C, Dermitzakis ET, Lyle R, Banfi S et al: Human chromosome 21 gene expression atlas in the mouse. Nature 2002, 420(6915):582-586.
63. Bortoluzzi S, Rampoldi L, Simionati B, Zimbello R, Barbon A, d'Alessi F, Tiso N, Pallavicini A, Toppo S, Cannata N et al: A comprehensive, high-resolution genomic transcript map of human skeletal muscle. Genome Res 1998, 8(8):817-825.
64. Versteeg R, van Schaik BD, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, van Kampen AH: The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Res 2003, 13:1998-2004.
65. Lercher MJ, Urrutia AO, Pavlicek A, Hurst LD: A unification of mosaic structures in the human genome. Hum Mol Genet 2003, 12:2411-2415.
66. Versteeg R, van Schaik BD, van Batenburg MF, Roos M, Monajemi R, Caron H, Bussemaker HJ, van Kampen AH: The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. Genome Res2003, 13(9):1998-2004.
67. Megy K, Audic S, Claverie JM: Positional clustering of differentially expressed genes on human chromosomes 20, 21 and 22. Genome Biol 2003, 4(2):P1.
68. Wei CL, Miura T, Robson P, Lim SK, Xu XQ, Lee MY, Gupta S, Stanton L, Luo Y, Schmitt J et al: Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state. Stem Cells 2005, 23(2):166-185.
69. Pallavicini A, Zimbello R, Tiso N, Muraro T, Rampoldi L, Bortoluzzi S, Valle G, Lanfranchi G, Danieli GA: The preliminary transcript map of a human skeletal muscle. Hum Mol Genet 1997, 6(9):1445-1450.
70. Silver LM: The peculiar journey of a selfish chromosome: mouse t haplotypes and meiotic drive. Trends Genet 1993, 9(7):250-254.
71. Papaioannou VE, Silver LM: The T-box gene family. Bioessays 1998, 20(1):9-19.
72. Vogel JH, von Heydebreck A, Purmann A, Sperling S: Chromosomal clustering of a human transcriptome reveals regulatory background. BMC Bioinformatics 2005, 6:230.
73. Lercher MJ, Urrutia AO, Hurst LD: Clustering of housekeeping genes provides a unified model of gene order in the human genome. Nat Genet 2002, 31:180-183.
74. Li Q, Lee BT, Zhang L: Genome-scale analysis of positional clustering of mouse testis-specific genes. BMC Genomics 2005, 6(1):7.
75. Divina P, Vlcek C, Strnad P, Paces V, Forejt J: Global transcriptome analysis of the C57BL/6J mouse testis by SAGE: evidence for nonrandom gene order. BMC Genomics 2005, 6(1):29.
76. Paillisson A, Dade S, Callebaut I, Bontoux M, Dalbies-Tran R, Vaiman D, Monget P: Identification, characterization and metagenome analysis of oocyte-specific genes organized in clusters in the mouse genome. BMC Genomics 2005, 6(1):76.
77. Yamashita T, Honda M, Takatori H, Nishino R, Hoshino N, Kaneko S: Genome-wide transcriptome mapping analysis identifies organ-specific gene expression patterns along human chromosomes. Genomics 2004, 84(5):867-875.
78. Yin YB, Zhang Y, Yu P, Luo JC, Jiang Y, Li SG: Comparative study of apoptosis-related gene loci in human, mouse and rat genomes. Acta Biochim Biophys Sin (Shanghai) 2005, 37(5):341-348.
79. Miller MA, Cutter AD, Yamamoto I, Ward S, Greenstein D: Clustered organization of reproductive genes in the C. elegans genome. Curr Biol 2004, 14(14):1284-1290.
80. Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, Paigen K: Evidence of a large-scale functional organization of mammalian chromosomes. PLoS Genet 2005, 1(3):e33.
81. Johnnidis JB, Venanzi ES, Taxman DJ, Ting JP, Benoist CO, Mathis DJ:Chromosomal clustering of genes controlled by the aire transcription factor. Proc Natl Acad Sci U S A 2005, 102(20):7233-7238.
82. Lee JM, Sonnhammer EL: Genomic gene clustering analysis of pathways in eukaryotes. Genome Res 2003, 13(5):875-882.
83. Allocco DJ, Kohane IS, Butte AJ: Quantifying the relationship between co-expression, co-regulation and gene function. BMC Bioinformatics 2004, 5:18.
84. Yanai I, Korbel JO, Boue S, McWeeney SK, Bork P, Lercher MJ: Similar gene expression profiles do not imply similar tissue functions. Trends Genet 2006, 22(3):132-138.
85. Hurst LD, Lercher MJ: Unusual linkage patterns of ligands and their cognate receptors indicate a novel reason for non-random gene order in the human genome. BMC Evol Biol 2005, 5:62.
86. Singer GA, Lloyd AT, Huminiecki LB, Wolfe KH: Clusters of co-expressed genes in mammalian genomes are conserved by natural selection. Mol Biol Evol 2005, 22(3):767-775.
87. Semon M, Lobry JR, Duret L: No evidence for tissue-specific adaptation of synonymous codon usage in humans. Mol Biol Evol 2006, 23:523-529.
88. Kosak ST, Groudine M: Gene order and dynamic domains. Science 2004, 306(5696):644-647.
89. Kosak ST, Groudine M: Form follows function: The genomic organization of cellular differentiation. Genes Dev 2004, 18(12):1371-1384.
90. Kalmykova AI, Nurminsky DI, Ryzhov DV, Shevelyov YY: Regulated chromatin domain comprising cluster of co-expressed genes in Drosophila melanogaster. Nucleic Acids Res 2005, 33(5):1435-1444.
91. Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, Zhang J, Haug J, Li L: Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood 2003, 101:383-389.
92. Kanaya S, Yamada Y, Kinouchi M, Kudo Y, Ikemura T: Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessed by multivariate analysis. J Mol Evol 2001, 53:290-298.
93. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA: "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 2002, 298:597-600.
94. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR: A stem cell molecular signature. Science 2002, 298:601-604.
95. Kosak ST, Groudine M: Form follows function: The genomic organization of cellular differentiation. Genes Dev 2004, 18:1371-1384.
96. Ajamian F, Suuronen T, Salminen A, Reeben M: Upregulation of class II histone deacetylases mRNA during neural differentiation of cultured rat hippocampal progenitor cells. Neurosci Lett 2003, 346:57-60.
97. Rasmussen TP: Embryonic stem cell differentiation: a chromatinperspective. Reprod Biol Endocrinol 2003, 1:100.
98. Lee JH, Hart SR, Skalnik DG: Histone deacetylase activity is required for embryonic stem cell differentiation. Genesis 2004, 38:32-38.
99. Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ et al: Regulation of neuronal traits by a novel transcriptional complex. Neuron 2001, 31:353-365.
100. Takizawa T, Nakashima K, Namihira M, Ochiai W, Uemura A, Yanagisawa M, Fujita N, Nakao M, Taga T: DNA methylation is a critical cell-intrinsic determinant of astrocyte differentiation in the fetal brain. Dev Cell 2001, 1:749-758.
101. Song MR, Ghosh A: FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation. Nat Neurosci 2004, 7:229-235.
102. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH: A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 2004, 116:779-793.
103. Vinogradov AE: Noncoding DNA, isochores and gene expression: nucleosome formation potential. Nucleic Acids Res 2005, 33:559-563.
104. Bernardi G: The isochore organization of the human genome and its evolutionary history--a review. Gene 1993, 135:57-66.
105. Bernardi G: The human genome: organization and evolutionary history. Annu Rev Genet 1995, 29:445-476.
106. Vinogradov AE: Isochores and tissue-specificity. Nucleic Acids Res 2003, 31:5212-5220.
107. Hiratani I, Leskovar A, Gilbert DM: Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A 2004,
101:16861-16866.
1. Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D: Ultraconserved elements in the human genome. Science 2004, 304(5675):1321-1325.
2. Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S et al: Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 2005, 15(8):1034-1050.
3. Fitch WM: Distinguishing homologous from analogous proteins. Syst Zool 1970, 19(2):99-113.
4. Koonin EV, Mushegian AR, Bork P: Non-orthologous gene displacement. Trends Genet 1996, 12(9):334-336.
5. Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH: Role of duplicate genes in genetic robustness against null mutations. Nature 2003, 421(6918):63-66.
6. Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H et al: Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 1999, 285(5429):901-906.
7. Gibson TJ, Spring J: Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding multidomain proteins. Trends Genet 1998, 14(2):46-49; discussion 49-50.
8. Tatusov RL, Koonin EV, Lipman DJ: A genomic perspective on protein families. Science 1997, 278(5338):631-637.
9. Tatusov RL, Galperin MY, Natale DA, Koonin EV: The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res 2000, 28(1):33-36.
10. Dessimoz C, Boeckmann B, Roth AC, Gonnet GH: Detecting non-orthology in the COGs database and other approaches grouping orthologs using genome-specific best hits. Nucleic Acids Res 2006, 34(11):3309-3316.
11. Rao M: Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells. Dev Biol 2004, 275:269-286.
12. Hoegg S, Meyer A: Hox clusters as models for vertebrate genome evolution. Trends Genet 2005, 21(8):421-424.
13. Li WH, Yang J, Gu X: Expression divergence between duplicate genes. Trends Genet 2005, 21(11):602-607.
14. Planet PJ: Tree disagreement: measuring and testing incongruence in phylogenies. J Biomed Inform 2006, 39(1):86-102.
15. Horiike T, Hamada K, Kanaya S, Shinozawa T: Origin of eukaryotic cell nuclei by symbiosis of Archaea in Bacteria is revealed by homology-hit analysis. Nat Cell Biol 2001, 3(2):210-214.
16. Noda AO, Ikeo K, Gojobori T: Comparative genome analyses of nervous system-specific genes. Gene 2006, 365:130-136.
17. Masatoshi Nei SK: Molecular Evolution and Phylogenetics: Oxford University Press, Inc.; 2000.
18. Kimura M: On the probability of fixation of mutant genes in a population. Genetics 1962, 47:713-719.
19. Wen-Hsiung Li DG: Fundamentals of Molecular Evolution. Sunderland Massachusetts: Sinauer Associates, INC. Publisher; 1991.
20. Kimura M: Evolutionary rate at the molecular level. Nature 1968, 217:624-626.
21. Chamary JV, Parmley JL, Hurst LD: Hearing silence: non-neutral evolution at synonymous sites in mammals. Nat Rev Genet 2006, 7:98-108.
22. Miyata T, Hayashida H: Extraordinarily high evolutionary rate of pseudogenes: evidence for the presence of selective pressure against changes between synonymous codons. Proc Natl Acad Sci U S A 1981, 78(9):5739-5743.
23. Nei M, Gojobori T: Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 1986, 3:418-426.
24. Pamilo P, Bianchi NO: Evolution of the Zfx and Zfy genes: rates and interdependence between the genes. Mol Biol Evol 1993, 10(2):271-281.
25. Comeron JM: A method for estimating the numbers of synonymous and nonsynonymous substitutions per site. J Mol Evol 1995, 41(6):1152-1159.
26. Muse SV: Estimating synonymous and nonsynonymous substitution rates. Mol Biol Evol 1996, 13(1):105-114.
27. Feng DF, Doolittle RF: Converting amino acid alignment scores into measures of evolutionary time: a simulation study of various relationships. J Mol Evol 1997, 44(4):361-370.
28. Grishin NV: Estimation of the number of amino acid substitutions per site when the aubatitution rate varies among sites. J Mol Evol 1995, 41:675-679.
29. Fraser HB, Hirsh AE, Steinmetz LM, Scharfe C, Feldman MW: Evolutionary rate in the protein interaction network. Science 2002, 296(5568):750-752.
30. Wilson AC, Carlson SS, White TJ: Biochemical evolution. Annu Rev Biochem 1977, 46:573-639.
31. Hurst LD, Smith NG: Do essential genes evolve slowly? Curr Biol 1999, 9(14):747-750.
32. Hurst LD, Williams EJ: Covariation of GC content and the silent site substitution rate in rodents: implications for methodology and for the evolution of isochores. Gene 2000, 261:107-114.
33. Smith NG, Hurst LD: The effect of tandem substitutions on the correlation between synonymous and nonsynonymous rates in rodents. Genetics 1999, 153:1395-1402.
34. Duret L, Mouchiroud D: Determinants of substitution rates in mammalian genes: expression pattern affects selection intensity but not mutation rate. Mol Biol Evol 2000, 17:68-74.
35. Wolfe KH, Sharp PM: Mammalian gene evolution: nucleotide sequence divergence between mouse and rat. J Mol Evol 1993, 37:441-456.
36. Kimura M, Ota T: On some principles governing molecular evolution. Proc Natl Acad Sci U S A 1974, 71(7):2848-2852.
37. Hirsh AE, Fraser HB: Protein dispensability and rate of evolution. Nature 2001, 411(6841):1046-1049.
38. Yang J, Gu Z, Li WH: Rate of protein evolution versus fitness effect of gene deletion. Mol Biol Evol 2003, 20(5):772-774.
39. Castillo-Davis CI, Hartl DL: Conservation, relocation and duplication in genome evolution. Trends Genet 2003, 19(11):593-597.
40. Pal C, Papp B, Hurst LD: Highly expressed genes in yeast evolve slowly. Genetics 2001, 158:927-931.
41. Subramanian S, Kumar S: Gene expression intensity shapes evolutionary rates of the proteins encoded by the vertebrate genome. Genetics 2004, 168:373-381.
42. Zhang L, Li WH: Mammalian housekeeping genes evolve more slowly than tissue-specific genes. Mol Biol Evol 2004, 21:236-239.
43. Krylov DM, Wolf YI, Rogozin IB, Koonin EV: Gene loss, protein sequence divergence, gene dispensability, expression level, and interactivity are correlated in eukaryotic evolution. Genome Res 2003, 13:2229-2235.
44. Pal C, Papp B, Hurst LD: Genomic function: Rate of evolution and gene dispensability. Nature 2003, 421(6922):496-497; discussion 497-498.
45. Jordan IK, Rogozin IB, Wolf YI, Koonin EV: Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res 2002, 12(6):962-968.
46. Rocha EP, Danchin A: An analysis of determinants of amino acids substitution rates in bacterial proteins. Mol Biol Evol 2004, 21(1):108-116.
47. Zhang J, He X: Significant impact of protein dispensability on the instantaneous rate of protein evolution. Mol Biol Evol 2005, 22(4):1147-1155.
48. Fraser HB, Wall DP, Hirsh AE: A simple dependence between protein evolution rate and the number of protein-protein interactions. BMC Evol Biol 2003, 3:11.
49. Jordan IK, Wolf YI, Koonin EV: No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly. BMC Evol Biol 2003, 3:1.
50. Walker DR, Koonin EV: SEALS: a system for easy analysis of lots of sequences. Proc Int Conf Intell Syst Mol Biol 1997, 5:333-339.
51. Koski LB, Golding GB: The closest BLAST hit is often not the nearest neighbor. J Mol Evol 2001, 52(6):540-542.
52. Bloom JD, Adami C: Apparent dependence of protein evolutionary rate on number of interactions is linked to biases in protein-protein interactions data sets. BMC Evol Biol 2003, 3:21.
53. Bloom JD, Adami C: Evolutionary rate depends on number ofprotein-protein interactions independently of gene expression level: response. BMC Evol Biol 2004, 4:14.
54. Fraser HB, Hirsh AE: Evolutionary rate depends on number of protein-protein interactions independently of gene expression level. BMC Evol Biol 2004, 4:13.
55. Saeed R, Deane CM: Protein protein interactions, evolutionary rate, abundance and age. BMC Bioinformatics 2006, 7:128.
56. Kuma K, Iwabe N, Miyata T: Functional constraints against variations on molecules from the tissue level: slowly evolving brain-specific genes demonstrated by protein kinase and immunoglobulin supergene families. Mol Biol Evol 1995, 12(1):123-130.
57. Wyckoff GJ, Wang W, Wu CI: Rapid evolution of male reproductive genes in the descent of man. Nature 2000, 403(6767):304-309.
58. Panhuis TM, Swanson WJ: Molecular evolution and population genetic analysis of candidate female reproductive genes in Drosophila. Genetics 2006, 173(4):2039-2047.
59. Hurst LD, Ellegren H: Sex biases in the mutation rate. Trends Genet 1998, 14(11):446-452.
60. Comeron JM: Selective and mutational patterns associated with gene expression in humans: influences on synonymous composition and intron presence. Genetics 2004, 167:1293-1304.
61. Doolittle RF, Feng DF, Johnson MS, McClure MA: Relationships of human protein sequences to those of other organisms. Cold Spring Harb Symp Quant Biol 1986, 51 Pt 1:447-455.
62. Alba MM, Castresana J: Inverse relationship between evolutionary rate and age of mammalian genes. Mol Biol Evol 2005, 22(3):598-606.
63. Elhaik E, Sabath N, Graur D: The "inverse relationship between evolutionary rate and age of mammalian genes" is an artifact of increased genetic distance with rate of evolution and time of divergence. Mol Biol Evol 2006, 23(1):1-3.
64. Fischer D, Eisenberg D: Finding families for genomic ORFans. Bioinformatics 1999, 15(9):759-762.
65. Dujon B: The yeast genome project: what did we learn? Trends Genet 1996, 12(7):263-270.
66. Cai JJ, Woo PC, Lau SK, Smith DK, Yuen KY: Accelerated evolutionary rate may be responsible for the emergence of lineage-specific genes in ascomycota. J Mol Evol 2006, 63(1):1-11.
67. Domazet-Loso T, Tautz D: An evolutionary analysis of orphan genes in Drosophila. Genome Res 2003, 13(10):2213-2219.
68. Daubin V, Ochman H: Bacterial genomes as new gene homes: the genealogy of ORFans in E. coli. Genome Res 2004, 14(6):1036-1042.
69. Drummond DA, Raval A, Wilke CO: A single determinant dominates the rate of yeast protein evolution. Mol Biol Evol 2006, 23(2):327-337.
70. McInerney JO: The causes of protein evolutionary rate variation. TrendsEcol Evol 2006, 21(5):230-232.
71. Wyckoff GJ, Malcom CM, Vallender EJ, Lahn BT: A highly unexpected strong correlation between fixation probability of nonsynonymous mutations and mutation rate. Trends Genet 2005, 21(7):381-385.
72. Hurst LD, Pal C: Evidence for purifying selection acting on silent sites in BRCA1. Trends Genet 2001, 17:62-65.
73. Xing Y, Lee C: Can RNA selection pressure distort the measurement of Ka/Ks? Gene 2006, 370:1-5.
74. Hellmann I, Zollner S, Enard W, Ebersberger I, Nickel B, Paabo S: Selection on human genes as revealed by comparisons to chimpanzee cDNA. Genome Res 2003, 13:831-837.
75. Smith NG, Hurst LD: Sensitivity of patterns of molecular evolution to alterations in methodology: a critique of Hughes and Yeager. J Mol Evol 1998, 47(4):493-500.
76. Chen FC, Vallender EJ, Wang H, Tzeng CS, Li WH: Genomic divergence between human and chimpanzee estimated from large-scale alignments of genomic sequences. J Hered 2001, 92(6):481-489.
77. Chamary JV, Hurst LD: Similar rates but different modes of sequence evolution in introns and at exonic silent sites in rodents: evidence for selectively driven codon usage. Mol Biol Evol 2004, 21:1014-1023.
78. Hughes AL, Yeager M: Comparative evolutionary rates of introns and exons in murine rodents. J Mol Evol 1997, 45:125-130.
79. Subramanian S, Kumar S: Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes. Genome Res 2003, 13(5):838-844.
80. Chen FC, Li WH: Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am J Hum Genet 2001, 68(2):444-456.
81. Lu J, Wu CI: Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee. Proc Natl Acad Sci U S A 2005, 102(11):4063-4067.
82. Smith NG, Hurst LD: The causes of synonymous rate variation in the rodent genome. Can substitution rates be used to estimate the sex bias in mutation rate? Genetics 1999, 152(2):661-673.
83. Keightley PD, Gaffney DJ: Functional constraints and frequency of deleterious mutations in noncoding DNA of rodents. Proc Natl Acad Sci U S A 2003, 100(23):13402-13406.
84. Majewski J, Ott J: Distribution and characterization of regulatory elements in the human genome. Genome Res 2002, 12(12):1827-1836.
85. Bustamante CD, Nielsen R, Hartl DL: A maximum likelihood method for analyzing pseudogene evolution: implications for silent site evolution in humans and rodents. Mol Biol Evol 2002, 19(1):110-117.
86. Wolfe KH, Sharp PM, Li WH: Mutation rates differ among regions of the mammalian genome. Nature 1989, 337:283-285.
87. Matassi G, Sharp PM, Gautier C: Chromosomal location effects on gene sequence evolution in mammals. Curr Biol 1999, 9(15):786-791.
88. Hurst LD, Pal C, Lercher MJ: The evolutionary dynamics of eukaryotic gene order. Nat Rev Genet 2004, 5(4):299-310.
89. Kumar S, Subramanian S: Mutation rates in mammalian genomes. Proc Natl Acad Sci U S A 2002, 99(2):803-808.
90. Casane D, Boissinot S, Chang BH, Shimmin LC, Li W: Mutation pattern variation among regions of the primate genome. J Mol Evol 1997, 45(3):216-226.
91. Nachman MW, Crowell SL: Estimate of the mutation rate per nucleotide in humans. Genetics 2000, 156(1):297-304.
92. Podlaha O, Zhang J: Nonneutral evolution of the transcribed pseudogene Makorin1-p1 in mice. Mol Biol Evol 2004, 21(12):2202-2209.
93. Fullerton SM, Bernardo Carvalho A, Clark AG: Local rates of recombination are positively correlated with GC content in the human genome. Mol Biol Evol 2001, 18:1139-1142.
94. Galtier N, Piganeau G, Mouchiroud D, Duret L: GC-content evolution in mammalian genomes: the biased gene conversion hypothesis. Genetics 2001, 159:907-911.
95. Galtier N: Gene conversion drives GC content evolution in mammalian histones. Trends Genet 2003, 19:65-68.
96. Meunier J, Duret L: Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 2004, 21:984-990.
97. Montoya-Burgos JI, Boursot P, Galtier N: Recombination explains isochores in mammalian genomes. Trends Genet 2003, 19:128-130.
98. Eyre-Walker A, Hurst LD: The evolution of isochores. Nat Rev Genet 2001, 2:549-555.
99. Bernardi G: Isochores and the evolutionary genomics of vertebrates. Gene 2000, 241:3-17.
100. Chen FC, Wang SS, Chen CJ, Li WH, Chuang TJ: Alternatively and Constitutively Spliced Exons Are Subject to Different Evolutionary Forces. Mol Biol Evol 2006, 23:675-682.
101. Yang Z: PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 1997, 13:555-556.
102. Sharp PM, Li WH: The rate of synonymous substitution in enterobacterial genes is inversely related to codon usage bias. Mol Biol Evol 1987, 4:222-230.
103. Sharp PM, Li WH: On the rate of DNA sequence evolution in Drosophila. J Mol Evol 1989, 28:398-402.
104. Shields DC, Sharp PM, Higgins DG, Wright F: "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol 1988, 5:704-716.
105. Powell JR, Moriyama EN: Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci U S A 1997, 94:7784-7790.
106. Ureta-Vidal A, L. Ettwiller, et al. : Comparative genomics: Genome-wide analysis in metazoan eukaryotes. Nat Rev Genet 2003, 4(4):251-262.
1. Bertuzzi F, Marzorati S, Secchi A: Islet cell transplantation. Curr Mol Med 2006, 6(4):369-374.
2. Slack JM: Developmental biology of the pancreas. Development 1995, 121(6):1569-1580.
3. D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE: Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 2006.
4. Shi Y, Hou L, Tang F, Jiang W, Wang P, Ding M, Deng H: Inducing embryonic stem cells to differentiate into pancreatic beta cells by a novel three-step approach with activin A and all-trans retinoic acid. Stem Cells 2005, 23(5):656-662.
5. Narushima M, Kobayashi N, Okitsu T, Tanaka Y, Li SA, Chen Y, Miki A, Tanaka K, Nakaji S, Takei K et al: A human beta-cell line for transplantation therapy to control type 1 diabetes. Nat Biotechnol 2005, 23(10):1274-1282.
6. Choi KS, Shin JS, Lee JJ, Kim YS, Kim SB, Kim CW: In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract. Biochem Biophys Res Commun 2005, 330(4):1299-1305.
7. Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ: In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 2004, 53(7):1721-1732.
8. Moriscot C, de Fraipont F, Richard MJ, Marchand M, Savatier P, Bosco D, Favrot M, Benhamou PY: Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells 2005, 23(4):594-603.
9. Deutsch G, Jung J, Zheng M, Lora J, Zaret KS: A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 2001, 128(6):871-881.
10. Burke Z, Oliver G: Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mech Dev 2002, 118(1-2):147-155.
11. Dabeva MD, Hurston E, Sharitz DA: Transcription factor and liver-specific mRNA expression in facultative epithelial progenitor cells of liver and pancreas. Am J Pathol 1995, 147(6):1633-1648.
12. Grompe M: Pancreatic-hepatic switches in vivo. Mech Dev 2003, 120(1):99-106.
13. Tosh D, Shen CN, Alison MR, Sarraf CE, Slack JM: Copper-deprivation in rats induces islet hyperplasia and hepatic metaplasia in the pancreas. Biol Cell 2006.
14. Ferber S, Halkin A, Cohen H, Ber I, Einav Y, Goldberg I, Barshack I, Seijffers R, Kopolovic J, Kaiser N et al: Pancreatic and duodenal homeobox gene 1 induces expression of insulin genes in liver and ameliorates streptozotocin-induced hyperglycemia. Nat Med 2000, 6(5):568-572.
15. Cao LZ, Tang DQ, Horb ME, Li SW, Yang LJ: High glucose is necessary for complete maturation of Pdx1-VP16-expressing hepatic cells into functional insulin-producing cells. Diabetes 2004, 53(12):3168-3178.
16. Zalzman M, Anker-Kitai L, Efrat S: Differentiation of human liver-derived, insulin-producing cells toward the beta-cell phenotype. Diabetes 2005, 54(9):2568-2575.
17. Drucker DJ: Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 2003, 17(2):161-171.
18. Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV: The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 2002, 32(1):128-134.
19. Hori Y, Gu X, Xie X, Kim SK: Differentiation of insulin-producing cells from human neural progenitor cells. PLoS Med 2005, 2(4):e103.
20. Shi CM, Cheng TM: Differentiation of dermis-derived multipotent cells into insulin-producing pancreatic cells in vitro. World J Gastroenterol 2004, 10(17):2550-2552.
21. Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB, Moritz W, Muller B, Vallejo M, Thomas MK, Habener JF: Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 2001, 50(3):521-533.
22. Seaberg RM, Smukler SR, Kieffer TJ, Enikolopov G, Asghar Z, Wheeler MB, Korbutt G, van der Kooy D: Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat Biotechnol 2004, 22(9):1115-1124.
23. Suzuki A, Oyama K, Fukao K, Nakauchi H, Taniguchi H: Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells. Cell Transplant 2002, 11(5):451-453.
24. Suzuki A, Nakauchi H, Taniguchi H: Prospective isolation of multipotent pancreatic progenitors using flow-cytometric cell sorting. Diabetes 2004, 53(8):2143-2152.
25. Ramiya VK, Maraist M, Arfors KE, Schatz DA, Peck AB, Cornelius JG: Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 2000, 6(3):278-282.
26. Bonner-Weir S, Taneja M, Weir GC, Tatarkiewicz K, Song KH, Sharma A, O'Neil JJ: In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 2000, 97(14):7999-8004.
27. Bonner-Weir S, Toschi E, Inada A, Reitz P, Fonseca SY, Aye T, Sharma A: The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr Diabetes 2004, 5 Suppl 2:16-22.
28. Todorov I, Nair I, Ferreri K, Rawson J, Kuroda A, Pascual M, Omori K, Valiente L, Orr C, Al-Abdullah I et al: Multipotent progenitor cells isolated from adult human pancreatic tissue. Transplant Proc 2005, 37(8):3420-3421.
29. Beattie GM, Otonkoski T, Lopez AD, Hayek A: Functional beta-cell mass after transplantation of human fetal pancreatic cells: differentiation or proliferation? Diabetes 1997, 46(2):244-248.
30. Hayek A, Beattie GM: Experimental transplantation of human fetal and adult pancreatic islets. J Clin Endocrinol Metab 1997, 82(8):2471-2475.
31. Beattie GM, Lopez AD, Otonkoski T, Hayek A: Transplantation of human fetal pancreas: fresh vs. cultured fetal islets or ICCS. J Mol Med 1999, 77(1):70-73.
32. Hayek A: In search of endocrine progenitor/stem cells in the human pancreas. Pediatr Diabetes 2004, 5 Suppl 2:70-74.
33. Hayek A: Cell replacement in type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2005, 18 Suppl 1:1157-1161.
34. Huang H, Tang X: Phenotypic determination and characterization of nestin-positive precursors derived from human fetal pancreas. Lab Invest 2003, 83(4):539-547.
35. Zhang L, Hong TP, Hu J, Liu YN, Wu YH, Li LS: Nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J Gastroenterol 2005, 11(19):2906-2911.
36. Maria-Engler SS, Correa-Giannella ML, Labriola L, Krogh K, Colin C, Lojudice FH, Aita CA, de Oliveira EM, Correa TC, da Silva IC et al: Co-localization of nestin and insulin and expression of islet cell markers in long-term human pancreatic nestin-positive cell cultures. J Endocrinol 2004, 183(3):455-467.
37. Abraham EJ, Kodama S, Lin JC, Ubeda M, Faustman DL, Habener JF: Human pancreatic islet-derived progenitor cell engraftment in immunocompetent mice. Am J Pathol 2004, 164(3):817-830.
38. Choi Y, Ta M, Atouf F, Lumelsky N: Adult pancreas generates multipotent stem cells and pancreatic and nonpancreatic progeny. Stem Cells 2004, 22(6):1070-1084.
39. Weir GC, Bonner-Weir S: Beta-cell precursors--a work in progress. Nat Biotechnol 2004, 22(9):1095-1096.
40. Yamamoto T, Yamato E, Taniguchi H, Shimoda M, Tashiro F, Hosoi M, Sato T, Fujii S, Miyazaki JI: Stimulation of cAMP signalling allows isolation of clonal pancreatic precursor cells from adult mouse pancreas. Diabetologia 2006, 49(10):2359-2367.
41. Dor Y, Brown J, Martinez OI, Melton DA: Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004, 429(6987):41-46.
42. Levine F, Mercola M: No pancreatic endocrine stem cells? N Engl J Med2004, 351(10):1024-1026.
43. Wang X, Hu J, Zhao D, Wang G, Tan L, Du L, Yang J, Hou L, Zhang H, Yu Y et al: NestinnegCD24low/- population from fetal Nestin-EGFP transgenic mice enriches the pancreatic endocrine progenitor cells. Pancreas 2005, 31(4):385-391.
44. Treutelaar MK, Skidmore JM, Dias-Leme CL, Hara M, Zhang L, Simeone D, Martin DM, Burant CF: Nestin-lineage cells contribute to the microvasculature but not endocrine cells of the islet. Diabetes 2003, 52(10):2503-2512.
45. Delacour A, Nepote V, Trumpp A, Herrera PL: Nestin expression in pancreatic exocrine cell lineages. Mech Dev 2004, 121(1):3-14.
46. Street CN, Lakey JR, Seeberger K, Helms L, Rajotte RV, Shapiro AM, Korbutt GS: Heterogenous expression of nestin in human pancreatic tissue precludes its use as an islet precursor marker. J Endocrinol 2004, 180(2):213-225.
47. Selander L, Edlund H: Nestin is expressed in mesenchymal and not epithelial cells of the developing mouse pancreas. Mech Dev 2002, 113(2):189-192.
48. Klein T, Ling Z, Heimberg H, Madsen OD, Heller RS, Serup P: Nestin is expressed in vascular endothelial cells in the adult human pancreas. J Histochem Cytochem 2003, 51(6):697-706.
49. Gu G, Brown JR, Melton DA: Direct lineage tracing reveals the ontogeny of pancreatic cell fates during mouse embryogenesis. Mech Dev 2003, 120(1):35-43.
50. Gu G, Dubauskaite J, Melton DA: Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 2002, 129(10):2447-2457.
51. Laconi E, Oren R, Mukhopadhyay DK, Hurston E, Laconi S, Pani P, Dabeva MD, Shafritz DA: Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol 1998, 153(1):319-329.
52. Guo D, Fu T, Nelson JA, Superina RA, Soriano HE: Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride. Transplantation 2002, 73(11):1818-1824.
53. Petersen BE, Zajac VF, Michalopoulos GK: Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 1998, 27(4):1030-1038.
54. Sell S: Heterogeneity and plasticity of hepatocyte lineage cells. Hepatology 2001, 33(3):738-750.
55. Beattie GM, Cirulli V, Lopez AD, Hayek A: Ex vivo expansion of human pancreatic endocrine cells. J Clin Endocrinol Metab 1997, 82(6):1852-1856.
56. Gao R, Ustinov J, Korsgren O, Otonkoski T: In vitro neogenesis of human islets reflects the plasticity of differentiated human pancreatic cells. Diabetologia 2005, 48(11):2296-2304.
57. Lechner A, Nolan AL, Blacken RA, Habener JF: Redifferentiation of insulin-secreting cells after in vitro expansion of adult human pancreatic islet tissue. Biochem Biophys Res Commun 2005, 327(2):581-588.
58. Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM: Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science 2004, 306(5705):2261-2264.
59. Eberhardt M, Salmon P, von Mach MA, Hengstler JG, Brulport M, Linscheid P, Seboek D, Oberholzer J, Barbero A, Martin I et al: Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochem Biophys Res Commun 2006, 345(3):1167-1176.
60. Gershengorn MC, Geras-Raaka E, Hardikar AA, Raaka BM: Are better islet cell precursors generated by epithelial-to-mesenchymal transition? Cell Cycle 2005, 4(3):380-382.
61. Duvillie B, Attali M, Aiello V, Quemeneur E, Scharfmann R: Label-retaining cells in the rat pancreas: location and differentiation potential in vitro. Diabetes 2003, 52(8):2035-2042.
62. Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A: Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999, 97(6):703-716.
63. Dahlstrand J, Zimmerman LB, McKay RD, Lendahl U: Characterization of the human nestin gene reveals a close evolutionary relationship to neurofilaments. J Cell Sci 1992, 103 ( Pt 2):589-597.
64. Lendahl U, Zimmerman LB, McKay RD: CNS stem cells express a new class of intermediate filament protein. Cell 1990, 60(4):585-595.
65. Hunziker E, Stein M: Nestin-expressing cells in the pancreatic islets of Langerhans. Biochem Biophys Res Commun 2000, 271(1):116-119.
66. Zhang L, Hu J, Hong TP, Liu YN, Wu YH, Li LS: Monoclonal side population progenitors isolated from human fetal pancreas. Biochem Biophys Res Commun 2005, 333(2):603-608.
67. Lechner A, Leech CA, Abraham EJ, Nolan AL, Habener JF: Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter. Biochem Biophys Res Commun 2002, 293(2):670-674.
68. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E: Defining the epithelial stem cell niche in skin. Science 2004, 303(5656):359-363.
69. Al-Abdullah IH, Ayala T, Panigrahi D, Kumar RM, Kumar MS: Neogenesis of pancreatic endocrine cells in copper-deprived rat models. Pancreas 2000, 21(1):63-68.
70. Waguri M, Yamamoto K, Miyagawa JI, Tochino Y, Yamamori K, Kajimoto Y, Nakajima H, Watada H, Yoshiuchi I, Itoh N et al: Demonstration of two different processes of beta-cell regeneration in a new diabetic mouse model induced by selective perfusion of alloxan. Diabetes 1997,46(8):1281-1290.
71. Lee CS, De Leon DD, Kaestner KH, Stoffers DA: Regeneration of pancreatic islets after partial pancreatectomy in mice does not involve the reactivation of neurogenin-3. Diabetes 2006, 55(2):269-272.
72. Bonner-Weir S, Baxter LA, Schuppin GT, Smith FE: A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development. Diabetes 1993, 42(12):1715-1720.
73. Beattie GM, Levine F, Mally MI, Otonkoski T, O'Brien JS, Salomon DR, Hayek A: Acid beta-galactosidase: a developmentally regulated marker of endocrine cell precursors in the human fetal pancreas. J Clin Endocrinol Metab 1994, 78(5):1232-1240.
74. Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J: Identification of a neural stem cell in the adult mammalian central nervous system. Cell 1999, 96(1):25-34.
75. Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD: Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 2001, 3(9):778-784.
76. Fernandes KJ, McKenzie IA, Mill P, Smith KM, Akhavan M, Barnabe-Heider F, Biernaskie J, Junek A, Kobayashi NR, Toma JG et al: A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol 2004, 6(11):1082-1093.
77. Tropepe V, Sibilia M, Ciruna BG, Rossant J, Wagner EF, van der Kooy D: Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Dev Biol 1999, 208(1):166-188.
78. Lammert E, Brown J, Melton DA: Notch gene expression during pancreatic organogenesis. Mech Dev 2000, 94(1-2):199-203.
79. Lee KM, Yasuda H, Hollingsworth MA, Ouellette MM: Notch 2-positive progenitors with the intrinsic ability to give rise to pancreatic ductal cells. Lab Invest 2005, 85(8):1003-1012.
80. Katoh M, Katoh M: Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells. Int J Mol Med 2006, 17(4):681-685.
81. Murtaugh LC, Stanger BZ, Kwan KM, Melton DA: Notch signaling controls multiple steps of pancreatic differentiation. Proc Natl Acad Sci U S A 2003, 100(25):14920-14925.
82. Apelqvist A, Li H, Sommer L, Beatus P, Anderson DJ, Honjo T, Hrabe de Angelis M, Lendahl U, Edlund H: Notch signalling controls pancreatic cell differentiation. Nature 1999, 400(6747):877-881.
83. Fujikura J, Hosoda K, Iwakura H, Tomita T, Noguchi M, Masuzaki H, Tanigaki K, Yabe D, Honjo T, Nakao K: Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas. Cell Metab 2006, 3(1):59-65.
84. Chenn A, Walsh CA: Regulation of cerebral cortical size by control of cellcycle exit in neural precursors. Science 2002, 297(5580):365-369.
85. Zechner D, Fujita Y, Hulsken J, Muller T, Walther I, Taketo MM, Crenshaw EB, 3rd, Birchmeier W, Birchmeier C: beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol 2003, 258(2):406-418.
86. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cook JM, Willert K, Gaiano N et al: Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005, 6(3):314-322.
87. Trowbridge JJ, Xenocostas A, Moon RT, Bhatia M: Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation. Nat Med 2006, 12(1):89-98.
88. Trowbridge JJ, Moon RT, Bhatia M: Hematopoietic stem cell biology: too much of a Wnt thing. Nat Immunol 2006, 7(10):1021-1023.
89. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R et al: GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol 2003, 10(12):1255-1266.
90. Klein PS, Melton DA: A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 1996, 93(16):8455-8459.
91. Coghlan MP, Culbert AA, Cross DA, Corcoran SL, Yates JW, Pearce NJ, Rausch OL, Murphy GJ, Carter PS, Roxbee Cox L et al: Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol 2000, 7(10):793-803.
92. Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF: Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 2001, 412(6848):736-739.
93. Murayama A, Matsuzaki Y, Kawaguchi A, Shimazaki T, Okano H: Flow cytometric analysis of neural stem cells in the developing and adult mouse brain. J Neurosci Res 2002, 69(6):837-847.
94. Inada A, Nienaber C, Bonner-Weir S: Endogenous beta-galactosidase expression in murine pancreatic islets. Diabetologia 2006, 49(5):1120-1122.
95. Gothot A, van der Loo JC, Clapp DW, Srour EF: Cell cycle-related changes in repopulating capacity of human mobilized peripheral blood CD34(+) cells in non-obese diabetic/severe combined immune-deficient mice. Blood 1998, 92(8):2641-2649.
96. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature 2006, 439(7079):993-997.