绒山羊皮肤干细胞定位、迁移及次级毛囊生长期差异表达基因文库的构建与筛选
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摘要
本论文旨在研究绒山羊皮肤干细胞的分布位置及迁移轨迹,构建生长期和休止期次级毛囊差异表达基因文库,筛选与绒山羊次级毛囊生长相关的特异表达基因,从而揭示产绒动物不同类型的毛囊干细胞的行为特征、定位分布、相互关系,特别是尚未见报道的次级毛囊的干细胞生物学特性,为建立毛囊干细胞休眠、增殖、迁移、分化和决定等生命活动过程和机制的模式提供方法和理论依据。
选择体态相近、健康的周岁绒山羊,分成两组:标记BrdU的实验组和未标记BrdU的对照组。根据干细胞的慢周期特性,对绒山羊表皮细胞DNA进行BrdU标记,定期取背部皮样,4%多聚甲醛固定,常规石蜡包埋切片,免疫组化检测,结果前10周内BrdU结果呈阳性。8周,BrdU标记细胞主要位于初级、次级毛囊的毛球部,毛干也有分布;8~10周,BrdU标记细胞仅位于初、次级毛囊的外根鞘;10周后无阳性信号分布。选择BrdU标记8周和8~10周的绒山羊背部皮样,分离酶II 4℃消化3小时,分离完整毛囊。分别用分段培养法和IV型胶原粘附法对毛囊标记细胞(毛球部和毛囊中段)进行培养,能形成典型的干细胞克隆,且细胞直径较小,核质比较大,符合皮肤干细胞的形态学特征。用皮肤干细胞的标志分子P63对BrdU标记细胞进行免疫组化鉴定,发现BrdU标记滞留细胞呈阳性。以上结果证明BrdU标记滞留细胞即为皮肤干细胞,初步确定干细胞位于初级、次级毛囊的毛母质和外根鞘,在表皮基底层也有分布。
为进一步阐明次级毛囊周期性重建过程中干细胞分化启动-休眠的调控基因,以生长期和休止期次级毛囊为研究对象,利用抑制性消减杂交技术,构建了具有高消减效率的生长和休止期次级毛囊的cDNA文库。挑取20个阳性克隆,用Nested PCR Primer 1和2R进行PCR扩增,插入片段长度主要分布在250~1000 bp之间。
随机挑取正、反向两个差异表达基因文库中的单克隆各750个进行PCR扩增、测序,分别获得309条和344条有效序列,平均长度分别为693bp和596bp。将其进行同源性分析,各获得224个和300个nucleotide数据库中山羊及其他物种的已知存在序列同源。在EST数据库中分别找到76个、38个相似EST序列,还有9个和6个无同源性序列。在GenBank数据库共注册非冗余ESTs 126条,序列号为64970025~64970150。对已知功能基因的ESTs进行分类,正反库中细胞分裂类各为15个和13个、细胞信号类为44个和49个、细胞结构蛋白30个和52个、细胞防御类13个和21个、代谢类24个和46个、基因/蛋白表达类33个和37个、未分类的65个和82个。
在此基础上,进行了两次荧光交换的cDNA芯片杂交,以筛选差异表达基因。发现6个次级毛囊生长期的差异基因,其中上调基因3个,下调基因3个;10个次级毛囊休止期的差异基因,其中上调基因9个,下调基因1个。
总之,本研究首次用BrdU活体标记追踪的方法证明绒山羊初级、次级毛囊及表皮中均存在皮肤干细胞;首次建立了用SSH方法分离绒山羊次级毛囊生长和休止期差异表达基因的方法,并结合荧光交换的cDNA芯片杂交来筛选。所发现的差异表达基因对阐明绒山羊毛囊干细胞休眠维持和分化启动的可能分子机制、探索干细胞技术在将来动物分子育种和绒毛生产中应用的可能性提供方法和理论依据,但对这些差异表达的基因尤其是功能未知的基因在绒毛生长中的确切生物学功能仍需进一步深入研究。
The research was carried out to study the localization and migration of skin stem cells, to construct suppression subtractive hybridization(SSH) libraries of secondary follicles in anagen and to search some candidate genes involved in cashmere development in Inner Mongolia cashmere goat with cDNA micrarray. The information generated in this study can reveal behavior characteristic and orientation distribution of follicle stem cells, especially biological characteristics of secondary follicle stem cells, also can privide theoretical basis and method on buliding mechanism model of dormancy, migration, proliferation, differentiation, decision processes of follicle stem cells.
The healthy cashmere goats were divided into two groups: the test group labeled BrdU and the control group unlabeled BrdU.BrdU was injected intravenously for a total of two injections. According to skin stem cells characteristics of the slow cycle, skin samples were took from the back skin of the goats,fixed in 4% paraformaldehyde, embedded with paraffin and sectioned,detected by immunohistochemistry.BrdU could be detected only 10 weeks in Inner Mongolia cashmere goats and could be used for large animals in vivo short-term markers. Intraperitoneal injection 8 weeks, positive signals located mainly in hair bulb of primary and sencondary follicle,also in hair shaft. Intraperitoneal injection 8-10 weeks, positive signals obvirously decreased,only could be found in outer root sheath. After 10 weeks, almost no positive signals distribution. The back skin samples labeled BrdU for 8 and 10 weeks were incubated in 0.2% dispaseII at 4℃for 3h,isolated primary and secondary follicles under a dissecting microscope,then cultured label-retaining cells (LRC) of hair follicles(hair bulb and follicle midpiece) in vitro with segmentation culture method and collagen IV adhesion culture method respectively.The LRCs showed a large nuclear/cytoplasmic ratio and small size,and clonogenicity with the morphological characteristics of skin stem cells.To evaluate the BrdU LRCs, P63, a possible epidermal stem cell specific marker, was used. Immunohistochemical results idicated BrdU LRC were positive for P63. These results showed that BrdU LRCs were epidermal stem cells.The stem cells possiblly located in not only hair matrix and outer root sheath of primary,secondary follicle,but also the epidermal basal layer.
To further clarify the startup–dormancy control genes of stem cells during secondary follicle reconstruction periodically,forward-SSH library was performed with cDNA from secondary follicle in anagen as the“tester”and cDNA from secondary follicle in telogen as the“driver”. While reverse-SSH library was performed with cDNA from secondary follicle in telogen as the“tester”and cDNA from secondary follicle in anagen as the“driver”.The gene fragments were sequenced, and analyzed by bioinformatics. Two SSH libraries had been constructed successfully. Twenty positive clones were amplificated by using nested PCR primer 1 and 2R, the size of inserts was 250-1000bp.
309 genes and 344 genes were obtained respectively by DNA sequencing 750 clones picked randomly from two SSH libraries. Their average length were 693bp and 596bp.After nucleotide blast homological analysis,224 matched to known genes, seventy-six matched only to other ESTs in dbEST, and the remaining nine showed no match to any ESTs or known genes in forward-SSH library. While 300 matched to known genes, thirty-eight matched only to other ESTs in dbEST, and the remaining six showed no match to any ESTs or known genes in reverse-SSH library. 126 redundancy ESTs were registered in the GenBank,their accession numbers were 64970025~ 64970150. These were categorized into seven categories on the basis of gene function. They were divided into cell division(15,13), cell signaling/communication(44, 49),cell structure/motility(30,52),cell organism defense(13,21),metabolism(24,46),gene/protein expression(33,37) and unclassed (65,82).
On this basis, the exchange of two fluorescent hybridizations of the cDNA chip were used to screen specific differentially expressed genes. A total of six differentially expressed genes were found in anagen including three up-regulated genes and three down-regulated genes.While ten differentially expressed genes were found in telogen including nine up-regulated genes and one down-regulated gene.
In conclusion,it is the first time that stem cells are located in primary, secondary follicles and epidermis of cashmere goats by BrdU labeling method;it is the first time that differentially expressed genes in secondary follicles of anagen and telogen are isolated by SSH,combined with the exchange of fluorescent cDNA chip hybridization to screen differentially expressed genes.The results are useful for elucidating the possible molecular mechanism on keeping dormancy and starting differentiation by stem cells, but it is also necessary to elucidate biological functions of differentially expressed genes,especially genes with unknown functions.
选择体态相近、健康的周岁绒山羊,分成两组:标记BrdU的实验组和未标记BrdU的对照组。根据干细胞的慢周期特性,对绒山羊表皮细胞DNA进行BrdU标记,定期取背部皮样,4%多聚甲醛固定,常规石蜡包埋切片,免疫组化检测,结果前10周内BrdU结果呈阳性。8周,BrdU标记细胞主要位于初级、次级毛囊的毛球部,毛干也有分布;8~10周,BrdU标记细胞仅位于初、次级毛囊的外根鞘;10周后无阳性信号分布。选择BrdU标记8周和8~10周的绒山羊背部皮样,分离酶II 4℃消化3小时,分离完整毛囊。分别用分段培养法和IV型胶原粘附法对毛囊标记细胞(毛球部和毛囊中段)进行培养,能形成典型的干细胞克隆,且细胞直径较小,核质比较大,符合皮肤干细胞的形态学特征。用皮肤干细胞的标志分子P63对BrdU标记细胞进行免疫组化鉴定,发现BrdU标记滞留细胞呈阳性。以上结果证明BrdU标记滞留细胞即为皮肤干细胞,初步确定干细胞位于初级、次级毛囊的毛母质和外根鞘,在表皮基底层也有分布。
为进一步阐明次级毛囊周期性重建过程中干细胞分化启动-休眠的调控基因,以生长期和休止期次级毛囊为研究对象,利用抑制性消减杂交技术,构建了具有高消减效率的生长和休止期次级毛囊的cDNA文库。挑取20个阳性克隆,用Nested PCR Primer 1和2R进行PCR扩增,插入片段长度主要分布在250~1000 bp之间。
随机挑取正、反向两个差异表达基因文库中的单克隆各750个进行PCR扩增、测序,分别获得309条和344条有效序列,平均长度分别为693bp和596bp。将其进行同源性分析,各获得224个和300个nucleotide数据库中山羊及其他物种的已知存在序列同源。在EST数据库中分别找到76个、38个相似EST序列,还有9个和6个无同源性序列。在GenBank数据库共注册非冗余ESTs 126条,序列号为64970025~64970150。对已知功能基因的ESTs进行分类,正反库中细胞分裂类各为15个和13个、细胞信号类为44个和49个、细胞结构蛋白30个和52个、细胞防御类13个和21个、代谢类24个和46个、基因/蛋白表达类33个和37个、未分类的65个和82个。
在此基础上,进行了两次荧光交换的cDNA芯片杂交,以筛选差异表达基因。发现6个次级毛囊生长期的差异基因,其中上调基因3个,下调基因3个;10个次级毛囊休止期的差异基因,其中上调基因9个,下调基因1个。
总之,本研究首次用BrdU活体标记追踪的方法证明绒山羊初级、次级毛囊及表皮中均存在皮肤干细胞;首次建立了用SSH方法分离绒山羊次级毛囊生长和休止期差异表达基因的方法,并结合荧光交换的cDNA芯片杂交来筛选。所发现的差异表达基因对阐明绒山羊毛囊干细胞休眠维持和分化启动的可能分子机制、探索干细胞技术在将来动物分子育种和绒毛生产中应用的可能性提供方法和理论依据,但对这些差异表达的基因尤其是功能未知的基因在绒毛生长中的确切生物学功能仍需进一步深入研究。
The research was carried out to study the localization and migration of skin stem cells, to construct suppression subtractive hybridization(SSH) libraries of secondary follicles in anagen and to search some candidate genes involved in cashmere development in Inner Mongolia cashmere goat with cDNA micrarray. The information generated in this study can reveal behavior characteristic and orientation distribution of follicle stem cells, especially biological characteristics of secondary follicle stem cells, also can privide theoretical basis and method on buliding mechanism model of dormancy, migration, proliferation, differentiation, decision processes of follicle stem cells.
The healthy cashmere goats were divided into two groups: the test group labeled BrdU and the control group unlabeled BrdU.BrdU was injected intravenously for a total of two injections. According to skin stem cells characteristics of the slow cycle, skin samples were took from the back skin of the goats,fixed in 4% paraformaldehyde, embedded with paraffin and sectioned,detected by immunohistochemistry.BrdU could be detected only 10 weeks in Inner Mongolia cashmere goats and could be used for large animals in vivo short-term markers. Intraperitoneal injection 8 weeks, positive signals located mainly in hair bulb of primary and sencondary follicle,also in hair shaft. Intraperitoneal injection 8-10 weeks, positive signals obvirously decreased,only could be found in outer root sheath. After 10 weeks, almost no positive signals distribution. The back skin samples labeled BrdU for 8 and 10 weeks were incubated in 0.2% dispaseII at 4℃for 3h,isolated primary and secondary follicles under a dissecting microscope,then cultured label-retaining cells (LRC) of hair follicles(hair bulb and follicle midpiece) in vitro with segmentation culture method and collagen IV adhesion culture method respectively.The LRCs showed a large nuclear/cytoplasmic ratio and small size,and clonogenicity with the morphological characteristics of skin stem cells.To evaluate the BrdU LRCs, P63, a possible epidermal stem cell specific marker, was used. Immunohistochemical results idicated BrdU LRC were positive for P63. These results showed that BrdU LRCs were epidermal stem cells.The stem cells possiblly located in not only hair matrix and outer root sheath of primary,secondary follicle,but also the epidermal basal layer.
To further clarify the startup–dormancy control genes of stem cells during secondary follicle reconstruction periodically,forward-SSH library was performed with cDNA from secondary follicle in anagen as the“tester”and cDNA from secondary follicle in telogen as the“driver”. While reverse-SSH library was performed with cDNA from secondary follicle in telogen as the“tester”and cDNA from secondary follicle in anagen as the“driver”.The gene fragments were sequenced, and analyzed by bioinformatics. Two SSH libraries had been constructed successfully. Twenty positive clones were amplificated by using nested PCR primer 1 and 2R, the size of inserts was 250-1000bp.
309 genes and 344 genes were obtained respectively by DNA sequencing 750 clones picked randomly from two SSH libraries. Their average length were 693bp and 596bp.After nucleotide blast homological analysis,224 matched to known genes, seventy-six matched only to other ESTs in dbEST, and the remaining nine showed no match to any ESTs or known genes in forward-SSH library. While 300 matched to known genes, thirty-eight matched only to other ESTs in dbEST, and the remaining six showed no match to any ESTs or known genes in reverse-SSH library. 126 redundancy ESTs were registered in the GenBank,their accession numbers were 64970025~ 64970150. These were categorized into seven categories on the basis of gene function. They were divided into cell division(15,13), cell signaling/communication(44, 49),cell structure/motility(30,52),cell organism defense(13,21),metabolism(24,46),gene/protein expression(33,37) and unclassed (65,82).
On this basis, the exchange of two fluorescent hybridizations of the cDNA chip were used to screen specific differentially expressed genes. A total of six differentially expressed genes were found in anagen including three up-regulated genes and three down-regulated genes.While ten differentially expressed genes were found in telogen including nine up-regulated genes and one down-regulated gene.
In conclusion,it is the first time that stem cells are located in primary, secondary follicles and epidermis of cashmere goats by BrdU labeling method;it is the first time that differentially expressed genes in secondary follicles of anagen and telogen are isolated by SSH,combined with the exchange of fluorescent cDNA chip hybridization to screen differentially expressed genes.The results are useful for elucidating the possible molecular mechanism on keeping dormancy and starting differentiation by stem cells, but it is also necessary to elucidate biological functions of differentially expressed genes,especially genes with unknown functions.
引文
1成令忠.钟翠平.蔡文琴主编.现代组织学[M].上海:上海科学技术文献出版社.2003.5
2 Gat U.Dasgupta R.Degenstein L,et al.Hair follicle morphogenesis and hair tumors in mice expressing a truncatedβ-catenin in skin[J].Cell.1998.95(5):605-614
3 Matsuzaki T.Yoshizato K.Role of hair papilla cells on induction and regeneration processes of hair follicles[J].Wound Repair and Regeneration.1998.6(6):524-530
4 Kumamoto T.Shalhevet D.Matsue H,et al.Hair follicles serve as local reservoirs of skin mast cell precursors[J].Blood.2003.102(5):1654-1660
5 Buli JJ.Muller-Rover S.Chronnell CM,et al.Contrasting expression patterns of CCAAT /enhancer-binding protein transcription factors in the hair follicle and at different stages of the hair growth cycle[J].J Invest Dermatol.2002.118(1):17-24
6 Paus R.Muller-R?ver S.Vander VC,et al.Comprehensive guide for the recognition and classification of distinct stage of hair follicle morphogenesis[J].Invest Dermatol. 1999.113(4):523-532
7 Nanba D.Hieda Y,et al.Remodeling of desmosomal and hemidesmosomal adhesion systems during early morphogenesis of mouse pelage hair follicles[J].Invest Dermatol.2000. 114:171-177
8 Hardy MH.The secret life of the hair follicle[J].Trends Genet.1992.8:55-61
9李国强.纪影畅.李宇.毛囊形态发生的分子机制[J].国外医学皮肤性病学分册.2004.30(1):38 -40
10 DasGupta R.Fuchs E.Multiple roles for activated LEF/TCF transcription complexes during hair follicle developmemt and differentiation[J].Development.1999.126:4557- 4568
11 St-Jacques B.DassuLe HR.Karavanova I,et al.Sonic hedgehog signaling is essential for hair development[J].Curr Biol.1998.8:1058-1068
12 Botchkarev VA.Botchkareva NV.Roth W,et al.Noggin is a mesenchymally derived stimulator of hair-follicle induction[J].Nat Cell Biol.1999.1(3):158-164
13 Reddy S.Andl T. Bagasra A,et al.Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis[J].Mech Dev.2001.107:69-82
14 Huelsken J.Vogel R.Erdmann B,et al.β-catenin Drivers hair follicle morphogenesis and stem cell differentiation in the skin[J].Cell.2001.105:533-545
15 Jamora C.DasGupta R.Kocieniewski P,et al.Links between signal transduction,trans- -cription and adhesion in epithelial bud development[J].Nature.2003.422 (6929):317-322
16 Yan MH.Wang LC.Sarah G,et al.Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors[J].Science.2000.290:523- 527
17 Kumar A.Eby M T.Sinha S,et al.The ectodermal dysplasia receptor activates the nuclear factor- B. JNK. and cell death pathways and binds to ectodysplasin A[J].Biol.Chem. 2001.276:2668-2677
18 Foitzik K.Paus R.Doetschman T,et al.The TGFβ2 isoform is both a required and sufficient inducer of murine hair follicle morphogenesis[J].Dev Biol.1999.212:278- 289
19 Massaque J.Chen YC. Driverling TGFβsignaling[J].Genes Dev.2000.14:627-644
20 Du Cros DL.Isaacs K.Moore GP.Localization of epidermal growth factor immunoreac- -tivity in sheep skin during wool follicle development[J].Invest Dermatol.1992.98: 109-115
21 Nanney LB.Magid M.Stoscheck CM,et al. Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages[J]. Invest Dermatol.1984.83:385-393
22 Wang LC.Liu ZY.Gambardella L,et al.Regular articles:conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration[J].Invest Dermatol.2000.114(5):901-908
23 Karlsson L.Bondjers C.Betsholtz C.Roles for PDGFA and sonic hedgehog in development of mesenchymal components of the hair follicle[J].Development.1999.126:2611-2621
24 Muller-Rover S.Handjiski B.Vander VC,et al.A comprehensive guide for the accurate classitifacation of murine hair follicles in distinct hair cycle stages[J].Invest Dermatol.2001.117(1):3-15
25 Ryder ML.Hair[M].London:Arnold.1973
26 Argyris TS.The effects of wounds on adjacent growing or resting hair follicles in mice[J].Arch Dermatol Symp.1956.61:31-36
27 Paus R. Muller-Rover S.and Botchkarev VA. Chronobiology of the hair follicle: hunting the“hair cycle clock”[J].Invest Dermatol.1999.4:338-345
28 Stenn KS and Paus R.What Drivers hair follicle cycling[J]?Exp Dermatol.1999.8:229- 236
29 Balsalobre A.Damiola F.Schibler U.A serum shock induces circadian gene expression in mammalian tissue culture cells[J].Cell.1998.93:929-937
30 Hardy MH.Van Exan RJ.Sonstegard KS,et al.Basal lamina changes during tissue interactions in hair follicles-an in vitro study of normal dermal papillae andvitamin A-induced glandular morphogenesis[J].Invest Dermatol.1983.80:27-34
31 Hardy MH.The differentiation of hair follicles and hairs in organ culture[J].Adv Biol Skin.1969.9:35-60
32 Maurer M.Peters EMJ.Botchkarev VA,et al.Intact hair follicle innervation is not essential for growth induction and development[J].Arch Dermatol Res.1998.290:574- 578
33宋志强.郝飞.毛乳头及毛囊生长调控的若干研究进展[J].重庆医学.2003.32(8):1087-1089
34 Stenn KS.Combates NJ.Eilertsen KJ,et al.Hair follicle growth drivers[J].Dermatol Clin.1996.14:543-558
35 Nagorcka BN and Mooney JR.The role of a reaction-diffusion system in the initiation of primary hair follicles[J].Theor Biol.1985.114:243-272
36 Risek B.Klier FG.and Gilula NB.Multiple gap junction genes are utilized during rat skin and hair development[J].Development.1992.116:639-651
37 Stenn KS and Paus R. Drivers of hair follicle cycling[J].Physilogical Reviews.2001. 81:449-494
38 Johnson E and Ebling FJ.The effect of plucking hairs during different phases of the follicuLar cycle[J].Embryol Exp Morphol.1964.12:465-474
39 Paus R.Muller-Rover S.and Mckay I.Driver of the hair follicle growth cycle.In:Hair Biology and Hair Growth Disorders[M].Price V.London:Dunitz.83-94
40 Chase HB.Growth of hair[J].Physiol Rev.1954.34:113-126
41 Argyris TS and Trimble ME.On the mechanism of hair growth stimulation in wound healing [J].Dev Biol.1964.9:230-254
42 Reynolds AJ and Jahoda CAB. Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis[J].Development.1993. 115:587-593
43 Paus R.Stenn KS.and Link RE.Telogen skin contains an inhibitor of hair growth[J].Br Dermatol.1990.122:777-784
44 Cotsarelis G.Sun TT.Link RE.Label-retaining cells reside in the bulge area of pilo- -sebaceous unit:implications for follicular stem cells,hair cycle and skin carino- -genesis[J].Cell.1990.61(7):1329-1337
45 Philpott MP.Paus R.Principles of hair follicle morphogenesis.Chuong CM.editor. Molecular basis of epithelial appendage morphogenesis[M].Landes Bioscience Publications.1998:75-103
46 Stenn K.Parimoo S.Growth of the hair follicle:a cycling and regenerating biological system.Chuong CM.editor.Molecular basis of epithelial appendage morphogenesis [M].Landes Bioscience Publications.1998:111-131
47 Paus R.Cotsarelis G.The biology of hair follicles[J].Med.1999.341:491-498
48 Alexeev V.Igoucheva O.Localized in vivo genotypic and phenotypic correction of the albino mutation in skin by RNA-DNA oligo nucleotide[J].Nature Biotechnol.2000.(18): 43-47
49吕中法.刘荣卿.细胞因子与毛囊生长周期[J].国外医学.生理、病理科学与临床分册.1999.19 (6):491-495
50屠军波.扬壮群.毛囊的体外培养及相关生长因子研究进展[J].中国美容医学.2001.10(4): 354-356
51 Hardy H.费伦奇.山羊[M].1983.1-28
52李金泉.绒山羊绒毛生长调控机理研究进展[J].中国草食动物.2001.21(3):41-43
53白俊艳.贾小平.李金泉.中国绒山羊育种研究进展[J].内蒙古农业科技.2006(2):20-22
54李金泉.内蒙古绒山羊育种原理与方法的研究[D].中国农业大学访问学者研究报告.2000:8-9
55尹俊.内蒙古绒山羊毛囊发育、生长周期及相关基因的研究[D].内蒙古大学.2004
56李长青.绒山羊毛囊周期性变化与生长期毛囊KAP13-1基因的表达[D].内蒙古农业大学.2005
57张燕军.内蒙古绒山羊皮肤毛囊发育规律及Hoxc9基因的研究[D].内蒙古农业大学.2007
58 Russel AJ.Fibre production from sheep and goats[J].The progress of sheep and research.1992.11:235-256
59贾志海.安民.山羊绒生长机理研究进展[J].草食家畜.1996.(1):2-6
60张春兰.内蒙古阿尔巴斯白绒山羊毛囊生长周期性变化与KAP6cDNA的特征分析[D].内蒙古农业大学.2003
61王永.郑玉才.龙虎等.中国山羊业研究[M].成都:四川科学技术出版社.1998:144-164
62 Mcdonald BJ.Hoey WA.Hopkins PS.Effect of photo-translocation on fleece growth in cashmere goats[J].Agric Res.1987.38:765-773
63税世荣.内蒙古绒山羊分布及其绒质绒量与生态条件的关系[J].内蒙古畜牧科学.1994(2):14 -17
64甄玉国.绒山羊生绒机理及其营养研究进展[J].内蒙古畜牧科学.2000.21(4):1-5
65 Johnson TJ.Rowe JB. Growth and cashmere production by goats in relation to dietary protein supply[C].Proceedings of the Australian Society of Animal Production.1984. 15:400-403
66李金泉.尹俊.绒山羊育种研究现状及展望[J].草食家畜.2001.1(3):19-23
67 Adelson DL.Cam GR.Desilva UF.Gene expression in sheep skin and wool(hair)[J]. Genomics.2004.83:95-105
68高爱琴.成纤维细胞生长因子5(FGF5)基因cDNA克隆及在不同品种绵羊和山羊中的多态性研究[D].内蒙古农业大学.2005
69席海燕.尹俊等.Hox基因Prox1在绒山羊皮肤中的表达[C].中国草食动物.2005-2006年全国养羊生产与学术研讨会议论文集.84-86
70赵珺.内蒙古绒山羊与蒙古绵羊BMP-2基因片段的克隆及表达[D].内蒙古农业大学.2006
71刘铮铸.山羊肌肉生长抑制素基因多态性及其与生产性能相关性研究[D].内蒙古农业大学. 2006
72张俊霞.山羊HGT KAP基因家族成员的克隆及其mRNA在皮肤中的表达[D].内蒙古农业大学. 2007
73李荣.内蒙古绒山羊BMP-4、BMPR-IB基因cDNA的克隆及BMPR-IB在皮肤毛囊中的表达[D].内蒙古农业大学.2007
74李玉荣.尹俊.张燕军等.绒山羊胚胎期和生长期皮肤毛囊差异表达基因研究[J].湖北农业科学.2008.47(2):146-148
75裴雪涛.干细胞生物学[M].北京:科学出版社.2003
76周家喜.人类和小鼠表皮干细胞的分离、鉴定和特性研究[D].中国科学院动物研究所.2004
77 Brouard M.Barrandon Y.Driverling skin morphogenesis:hope and despair[J].Curr Opin Biotechnol.2003.14(5):520-525
78 Bickenbach JR.Chism E.Selection and extended growth of murine epidermal stem cells in culture[J].Exp Cell Res.1998.244:184-195
79 Kaur P.Li A.Adhesive properties of human basal epidermal cells:an analysis of keratinocyte stem cells,transit amplifying cells and postmitotic differentiating cells[J].Invest Dermatol.2000.114(3):413-420
80 Jones PH.Isolation and characterization of human epidermal stem cells[J].Clin sci. 1996.91:141-146
81 Cotsarelis G.Kaur P.Dhouailly D,et al.Epithelial stem cells in the skin:definition, markers,localization and functions[J].Exp Dermatol.1999.8:80-88
82 Watt FM.Herde MD.Keratinocyte integrins.The keratinocyte handbook[M].Cambridge University Press.1994.153-164
83 Jones PH.Epithelial stem cells[J].1997.19:683-690
84 Brakebusch C.Richard G.Quondamatteo F,et al.Skin and hair follicle integrity is crucially dependent on integrinβexpression on keratinocytes[J].EMBO.2000.19: 3990-4003
85 Tani H.Morris RJ and Kaur P.Enrichment for murine keratinocyte stem cells based on cell surface phenotype[J].PNAS.2000.97:10960-10965
86 Li A.Simmons PJ.Kaur P.Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype[J].PNAS.1998.95:3902-3907
87 Lyle S.Christofidou SM.Liu Y,et al.The C8/144B monoclonal antibody recognizescytokeratin15 and defines the location of human hair follicle stem cells[J].Cell Sci.1998.111(21):3179-3188
88 Michel M.Torok N.Godbout MJ,et al.Keratin19 as a biochemical marker of skin stem cells in vivo and in vitro:Keratin19 expressing cells are differentially localized in function of anatomic sites,and their number varies with donor age and culture stage[J].Cell Sci.1996.109:1017-1028
89 Michel M. L'Heureux N.Auger FA,et al.From newborn to adult:phenotypic and functional properties of skin equivalent and human skin as a function of donor age[J].Cell Physio.1997.171:179-189
90 Lyle S.Christofidou SM.Liu Y,et al.Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype[J].Invest Dermatol Symp Proc. 1999.4(3):296-301
91 Pellegrini G.Dellambra E.Golisano O,et al.P63 identifies keratinocyte stem cells [J].PNAS.2001.98(6):3156-3161
92 Yang A.Schweitzer R.Sun D,et al.P63 is essential for regenerative proliferation in lumb,craniofacial and epithelial development[J].Nature.1999.398:714-718
93 Trempus CS.Morris RJ.Bortner CD,et al.Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34[J].Invest Dermatol.2003. 120(4):501-511
94 Matic M.Petrov IN.Chen S,et al.Stem cells of the corneal epithelium lack connexins and metabolite transfer capacity[J].Differentiation.1997(61):251-260
95 Ohyama M.Terunuma A.Tock CL,et a1.Characterization and isolation of stem cell enriched human hair follicle bulge cells[J].Clin Invest.2006.116:249-260
96 Scott EV and Ekel TM. Geometric relationships between the matrix of the hair bulb and its dermal papilla in normal and alopecic scalp[J].Invest Dermatol.1958.31:281- 287
97 Reynolds AJ and Jahoda CAB. Hair follicle stem cells? A distinct germinative epidermal cell popuLation is activated in vitro by the presence of hair dermal papilla cells[J]. Cell Sci.1991.99:373-385
98 Kobayashi K.Rochat A.Barrandon Y.Segregation of keratinocyte colony-forming cells in the bulge of the rat virissa[J].PNAS.1993.90(15):7391-7395
99 Rochat A.Kobayashi K.Barrandon Y.Location of stem cells of human hair follicles by clonal analysis[J].Cell.1994.76(6):1063-1073
100 Morris RJ.Potten CS.Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of growth[J].Invest Dermatol.1999.112(4):470-475
101 Taylor G.Lehrer MS.Jensen PJ,et al.Involvement of follicular stem cells in forming not only the follicle but also the epidermis[J].Cell.2000.102:451-461
102 Oshima H.Rochat A.Kedziaet C,et al.Morphogenesis and renewal of hair follicles from adult multipotent stem cells[J].Cell.2001.104(2):233-245
103 Tani H.Morris RJ.type[J].PNAS.2000.97(20):10960-10965
104 Dunnwald M.Tomanek CA.Alexandrunas D,et a1.Isolating a pure population of epidermal stem cells for use in tissue engineering[J].Exp Dermatol.2001.10(1):45-54
105 Schofield R.The relationship between the spleen colony-forming cell and the haemopoietic stem cell[J].Blood Cells.1978.4(1-2):7-25
106 Spradling A.Drummond BD.and Kai T.Stem cells find their niche[J].Nature.2001.414 (6859):98-104
107 Wagers AJ.Weissman IL. Plasticity of adult stem cells[J].Cell.2004.116(5):639-648
108 Lavker RM.Sun TT.Oshima H,et a1.Hair follicle stem cells[J].Investig Dermatol Symp Proc.2003.8(1):28-38
109 Tumbar T.Guasch G.GrecoV,et al.Defining the epithelial stem cell niche in skin[J]. Science.2004.303(5656):359-363
110 Blanpain C.Lowry WE.Geoghegan A,et al.Self-renewal,multipotency and the existence of two cell populations within an epithelial stem cell niche[J].Cell.2004.118(5): 635-648
111 Zhu AJ.Haase I.Watt FM.Signaling viaβ1-integrins and mitogenactivated protein kinase determines human epidermal stem cell fate in vitro[J].PNAS.1999.96:6728- 6733
112 Alonso L and Fuchs E.Stem cells in the skin:waste not,Wnt not[J].Genes Dev.2003. 17:1189
113 Fuchs E.Tumbar T and Guasch G. Socializing with the neighbors: stem cells and their niche[J].Cell.2004.116(6):769-778
114 Raghavan S.Bauer C.Mundschau G.et al.Conditional ablation ofβ1-integrin in skin: severe defects in epidermal proliferation.basement membrane formation and hair follicle invagination[J].Cell Biol.2000.150:1149-1160
115孙晓庆.付小兵.盛志勇.表皮干细胞[J].中华创伤杂志.2000.16(10):635-638
116 Logan CY.Nusse R.The Wnt signaling pathway in development and disease[J].Annu Rev Cell Dev Biol.2004.20:781-810
117 Andl T.Reddy ST.Gaddapara T,et al.WNT signals are required for the initiation of hair follicle development[J].Dev Cell.2002.2(5):643-653
118 Merrill BJ.Gat U.DasGupta R,et al.Tcf3 and Lef1 regulate lineage differentiationof multipotent stem cells in skin[J].Genes Dev.2001.15(13):1688-1705
119 Van MD.Kolligs FT.Dlugosz AA,et al.Transient activation ofβ-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice[J].Genes Dev.2003.17(10):1219-1224
120 Locelso C.Prowse DM.Watt FM.Transient activation ofβ-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours[J].Development.2004.131(8):1787-1799
121 Kanitakis J.Bourchany D.Faure M,et al.Expression of the hair stem cell-specific keratin15 in pilar tumors of the skin[J].Eur Dermatol.1999.9(5):363-365
122 Beaudoin GM.Sisk JM.CouLombe PA,et al.Hairless triggers reactivation of hair growth by promoting Wnt signaling[J].PNAS.2005.102(41):14653-14658
123 Braun KM.Niemann C.Jensen UB,et al.Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in whole mounts of mouse epidermis[J].Development.2003.130(21):5241-5255
124 Blanpain C.Fuchs E.Epidermal stem cells of the skin[J].Annu Rev Cell Dev Biol.2006. 22:339-373
125 Tsakonas SA.Rand MD.Lake RJ.Notch signaling:cell gate driver and signal integration in development[J].Science.1999.284:770-776
126 Lowell S.Jones P.Leroux I,et al. StimuLation of human epidermal differentiation by delta-notch sigalling at the boundaries of stem cell clusters[J].Curr Bio.2000. 10:491-500
127 Gandarillas A.Watt FM.c-Myc promotes differentiation of human epidermal stem cells [J].Genes Dev.1997.11(21):2869-2882
128 Willert K.Brown JD.Danenbrg E,et al.Wnt proteins are lipid-modified and can act as stem cell growth factors[J].Nature.2003.423(6938):448-452
129 Arnold I.Watt FM.c-Myc activation in transgenic mouse epidermis result in mobilization of stem cells and differentiation of their progeny[J].Curr Biol.2001. 11(8):558-568
130 Frye M.Gardner C.Li ER,et al.Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interaction with the local micro- environment[J].Development.2003.130(12):2793-2808
131 Niemann C.Owens DM.HuLsken J,et al.Expression of Delta N-Lef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours[J].Development.2002.129(1):95-109
132 Jamora C.Fuchs E.Intercellular adhesion.signaling and the cytoskeleton [J].Nat CellBiol.2002.4(4):E101-108
133 Honeycutt KA.Roop DR.c-Myc and epidermal stem cell fate determination[J]. Dermatol.2004.31(5):368-375
134 Fuchs E.Scratching the surface of skin development[J].Nature.2007.445(7130): 834-842
135 Zhang JW.He XC.Tong WG,et al.Bone morphogenetic protein signaling inhibits hair follicle growth induction by restricting epithelial stem/progenitor cell activation and expansion.Stem Cells[J].2006.24(12):2826-2839
136 Moore KA.Lemischka IR.Stem cells and their niches[J].Science.2006.311(5769):1880- 1885
137 Hashimoto A.Kurosaki M.Gotoh N.Shc regulates epidermal growth factor-induced activation of the JNK signaling pathway[J].Biol Chem.1999.274:20139-20143
138 Haase I.Evans R.Pofahl R,et al.Regulation of keratinocyte shape. migration and wound epithelialization by IGF1- and EGF-dependent signaling pathways[J].Cell Sci.2003. 116:3227-3238
139 Mann A.Breuhahn K.Schirmacher P,et al.Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing:stimulation of keratinocyte proliferation,granulation tissue formation and vascularization[J].Invest Derm. 2001.117:1382-1390
140 Ferrari G.Cusella G.Angelis D,et al. Muscle regeneration by bone marrow-derived myogenic progenitors[J].Science.1998.279:1528-1530
141 Brazelton TR.Rossi FMV.Keshte GI,et al.From marrow to brain:expression of neuronal phenotypes in adult mice[J].Science.2000.290:1775-1779
142 Krause DS.Theise ND.Collector MI,et al.Multi-organ,multi-lineage engraftement by a single bone marrow-derived stem cell[J].Cell.2001.105:369-377
143 Lagasse E.Connors H.Dhalimy MAl,et al.Purified hematopoietic stem cells can differentiate into hepatocytes in vivo[J].Nature Medicine.2000.6(11):1229-1234
144 Anderson DJ.Gage FH.Weissman IL.Can stem cells cross lineage boundaries?[J].Nat Med.2001.7(4):393-395
145 Bjornson CR.Rietze R L.ReynoldsB A,et al.Turning brain into blood:a hematopoietic fatead opted by adult neural stem cells in vivo[J].Science.1999.283:534-537
146 Sata M.Saiura A.Kunisato A,et al.Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis[J].Nature Medicine.2002.8(4):403-409
147 Liang L.Bickenbach JR.Somatic epidermal stem cells can produce multiple cell lineagesduring development[J].Stem cells.2002.20:21-31
148 Toma J G.Akhavan M.Fernandes JL.Isolation of multipotent aduLt stem cells from the dermis of mammalial skin[J].Nature Cell Biology.2001.3:778-784
149 Lako M.Armstrong L.Cairns PM,et al.Hair follicle dermal cells repopulate the mouse heamatopoietic system[J].Cell Sci.2002.115:3967-3974
150史春梦.真皮来源成体多能干细胞的生物学性状与促进创伤修复的实验研究[D].第三军医大学.2003
151杨学义.表皮干细胞建系及重建角膜缘干细胞缺损眼表研究[D].西北农林科技大学.2004
152史明艳.山羊毛囊干细胞及组织工程皮肤构建研究[D].西北农林科技大学.2006
153刘迎春.成年绒山羊皮肤干细胞的分离、纯化、鉴定与诱导[D].内蒙古农业大学.2007
154 Saiful Islam.MD.Isolation.Characterization and directional differentiation of skin stem cells derived from cashmere goat fetus[D].内蒙古农业大学.2007
155付小兵.方利君.王玉新等.骨髓间充质干细胞自体移植提高猪皮肤创面修复质量的初步研究[J].中华医学杂志.2004.84(11):920-923
156 Brouard M.Barrandon Y.Driverling skin morphogenesis:hope and despair[J].Current Opinion Biotechnol.2003.14(5):520-525
157 Kuhn U.Terunuma A.Pfutzner W,et al.In vivo assessment of gene delivery to keratinocytes by lentiviral vectors[J].J Virol.2002.76(3):1496-1504
158高艳红.裴雪涛.皮肤干细胞的研究现状与应用前景[J].中华烧伤杂志.2003.19(1):60-62
159 Lee SW.Tomasetto C and Sagar R.Positive selection of cadidate tumor-suppresser genes by subtractive hybridization[J].PNAS.1991.88:2825-2829
160 Liang P and Pardee AB.Differential display of eukaryotic messenger RNA by means of the Polymerase Chain Reaction[J].Science.1992.257(14):967-971
161 Shoham NG.Arad T.Rosin AR,et al.Differential display assay and analysis[J]. Biotechniques.1996.20(2):182-184
162 Zegzouti H.Jones B.Marty C,et al.Improved screening of cDNAs generated by mRNA differential display enables the selection of true positives and the isolation of weekly expressed messages[J].Plant Molecular Biology.1997.15:236-245
163 Lisitsyn N and Wigler M.Cloning the differences between two complex genomes[J]. Science.1993.259(5907):946-951
164 Diatchenko L.ChrisLau YF.Campbell AP,et al.Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries[J].PNAS.1996.93(12):6025-6030
165 Velculescu VE.Zhang L.Vogelstein B,et al.Serial analysis of gene expression[J]. 1995.270(5235):484-487
166 Richards M.Tan SP.Tan JH.The transcriptome profile of human embryonic stem cells as defined by SAGE[J].Stem Cells.2004.22(1):51-64
167 Quere R.Manchon L.Lejeune M,et al.Mining SAGE data allows large-scale,sensitive screening of antisense transcript expression[J].Nucleic Acids Res.2004.32.(20): e163(1-7)
168 Keime C.Damiola F.Mouchiroud D,et al.Identitag,a relational database for SAGE tag identification and interspecies comparison of SAGE libraries[J].BMC Bio informatics. 2004.5:143(1-12)
169 Boheler KR.Tarasov KV.SAGE analysis to identify embryonic stem cell-predominant transcripts[J].Methods Mol Biol.2006.329:195-221
170 Richards M.Tan SP.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[J].Stem Cells.2006.24(5):1162-1173
171 Kurian KM.Watson CJ and Wyllie AH.DNA chip technology[J].Pathol.1999.187(3):267- 271
172 Sheets MD.Amersdorfer P.Finnern R,et al.Efficient construction of a large nonimmune phage antibody liberary:The production of high-affinity human single-chain antibodies to protein antigens[J].PNAS.1998.95(11):6157-6162
173 Burioni R.Plaisant P.Bugli F,et al.A new subtraction technique for molecular clonging of rare antibody specifities from phage display libraries[J].Res.Virol.1998.149(5): 327-330
174 Guy GR.Philip R and Tan YH. Analysis of cellular phosphoproteins by two-dimensional gel electrophoresis:Applications for cell signaling in normal and cancer cells[J]. Elecophoresis.1994.15(3-4):417-440
175欧阳曙光.贺福初.生物信息学:生物实验数据和计算技术结合的新领域[J].科学通报.1994.44:1457-1468
176张春霆.生物信息学的现状与展望[J].世界科技研究与发展2000.(6):17-20
177 Rudert FG.Ilag L.Functional genomicswith protein-protein interactions[J].Biotech- nol.Annul.Rev.2000.(5):45-86
178 Samuel A.Jarrod C.Elia S,et al.Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes[J].Science.2002.(297):1301-1310
179胡志远.贺福初.蛋白质组研究进展[J].生物化学与生物物理进展.1999.(3):202-204
180尹文兵.黄勤妮.印莉萍.模式植物蛋白质组研究进展[J].生物信息学.2004.(2):47-50
181 Gierke P.Zhao C.Brackmann M.Expression analysis of members of the neuronal calciumsensor protein family:combining bioinformatics and western blot analysis[J]. Biochemical and Biophysical Research Communications.2004.(1):38-43
182王亚辉.世纪之交生物学发展的主要趋势[J].中国科学基金.2000.(3):167-168
183 Eric J.Current trends in bioinformatics[J].Trends in Biotechnology.2002.20(8): 317-319
184芮菊生.杜懋芩.陈海明等.组织切片技术[M].北京:人民卫生出版社.1980
185 Nixon AJ.A method for determining the activity state of hair follicles[J].Biotech Histochem.1993:68(6):316-325
186王伯沄.李玉松.黄高升等.病理学技术[M].北京:人民卫生出版社.2000
187安伟.内蒙古绒山羊毛囊的分离培养和类初级毛囊干细胞的分离及培养[D].内蒙古农业大学.2007
188黄文孝.肖红俊.汪吉宝等.用BrdU标记技术观察大鼠内淋巴囊的S期细胞[J].中国组织化学与细胞化学杂志.2002.11(4):4003
189 Gratzner HG. Monoclonal antibody to 5-bromo and 5-iododeoxyuridine:a new reagent for detection of DNA replication[J].Science.1982.218(4571):474-475
190 Nakamura S.Takeda Y.Kanno M,et al. Application of BrdU and anti-BrdU monoclonal antibody for the in vivo analysis of proliferative characteristics of human leukemia cells in bone marrow[J].Oncology.1991.48(4):285-289
191陈广平.郭慕依.陈琦等.应用BrdU单抗免疫组化染色观察大鼠系膜细胞生长情况[J].上海医科大学学报.1996.23(4):305-306
192 Xiang ZZ and Markel MD.Bromodeoxyuridine immunohistochemistry of epon-embedded undecalcified bone in a canine fracture healing model[J].Histochem Cytochem.1995. 43(6):629-635
193 Pollack A.Terry NH.Wu CS,et al.Specific staining of iododeoxyuridine and bromo- -deoxyuridine in tumors double labelled in vivo:a cell kinetic analysis[J]. Cytometry. 1995.20(1):53-61
194刘华庆.欧阳旭红.免疫组化的标准化[J].贵州医药.2001.25(8):754-755
195李甘地主编.组织病理技术[M].北京:人民卫生出版社.2002.43-47
196成娘.刘卫平.李甘地.用EDTA缓冲液做抗原修复增强ER.PR免疫组化染色[J].临床与实验病理学杂志.2001.17(3):274
197 Philpott MP.Green MR.Kealey T.Human hair growth in vitro[J].Cell Sci.1990.97:463- 471
198 Green MR.Clay CS.Gibson WT,et al.Rapid isolation in large numbers of intact,viable, individual hair follicles from skin:biochemical and ultrastructural characteri- -zation[J].Invest Dermatol.1986.87:768-770
199 Rogers G.Martinet N.Steinert P,et al.Cultivation of murine hair follicles as organoids in a collagen matrix[J].Invest Dermatol.1987.89:369-379
200 Misago N.Toda S.Sugihara H,et al.Proliferation and differentiation organoid hair follicle cells co-cultured with fat cells in collagen gel matrix culture[J].Br J Dermatol.1998.139(1):40-48
201武津津.刘荣卿.叶庆佾等.毛乳头细胞高效分离培养方法探索[J].中华皮肤科杂志.1997.30 (6):383-385
202程波.刘荣卿.武津津等.改良毛乳头细胞培养法[J].中华皮肤科杂志.2001.34(5):387-388
203 Ibraheem M.Galbratth H.Scaife J,et al.Growth and viability of secondary hair follicles of the Angora goat cultured in vitro[J].Anat.1993.182:231-238
204 Ibraheem M.Galbratth H.Scaife J.et al.Growth of secondary hair follicles of the Cashmere goat in vitro and their response to prolactin and melatonin[J]. Anat.1994. 185:135-142
205陈阅增主编.普通生物学[M].北京:高等教育出版社.1997
206 Parsa R.Yang A.McKeon F,et al.Association of P63 with proliferative potential in normal and neoplastic human keratinocytes[J].Invest Dermatol.1999.113(6):1099- 1105
207 L Li and T Xie.Stem cell niche:structure and function[J]. Annu Rev Cell Dev Biol. 2005. 21:605-631
208 Rizvi AZ and Wong MH.Epithelial stem cells and their niche:There’s no place like home.Stem Cells.2005.23:150-165
209 J.萨姆布鲁克.D.W.拉塞尔著.黄培堂等译.分子克隆实验指南[M].(第三版)北京:科学出版社.2002
210 Chenchik A.Zhu YY.Diatchenko L,et al.Generation and use of high-quality cDNA from small amounts of total RNA by SMART.In Gene Cloning and Analysis by RT- PCR(Bio Techniques Boods.MA)PP.305-319
211 Zhumabayeva B.Diatehenko L.Chenehik A,et a1.Use of SMARTTM generated cDNA for gene expression studies in multiple human tumors[J].Biotechniques.2001.30(1):158-163
212 Kuang WW.Thompson DA.Hoch RV,et al.Differential screening and suppression subtrac- -tive hybridization identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line[J].Nucleic Acids Res.1998.26(4):1116- 1123
213 Yang GP.Ross DT.Kuang WW,et al.Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes[J].Nucleic Acids Res.1999.27(6): 1517-1523
214 Girard JP.Baekkevold ES.Takeshi Yamanaka.et al.Heterogeneity of endothelial cells: The specialized phenotype of human high endothelial venules characterized by suppression subtractive hybridization[J].Am J Pathol.1999.155(6):2043-2055
215 Von SO.Thies WG.and Hofmann M.A high throughput screening for rarely transcribed differentially expressed genes[J].Nucleic Acids Res.1997.25:2598-2602
216张红缨.张今.PCR技术应用的新进展[J].生物化学与生物物理进展.1996.23(6):509-513
217 Clark JM.Novel nontemplated nucleotide addition reactions catalyzed by procaryotic and eucaryotic DNA polymerase[J].Nucl Acids Res.1988.16(20):9677-9686
218 Holton TA.Graham MW.A simple and efficient method for direct cloning of PCR products using ddT-Tailed vectors[J].Nucleic Acids Res.1991.19:1156-1158
219 Huang XQ.Madan A.CAP3:A DNA sequence assembly program[J].Genome Research.1999.9(9): 868-877
220 Newman T.Bruijn FJD.Green P,et al.Genes galore:Asummary of methods for accessing results from large-scale partial sequencing of anonymous arabidopsis cDNA clones [J].Plant Physiology.1994.106(4):1241-1255
221 Anderson I.Brass A.Searching DNA database for similarities to DNA sequenses:when is a match significant?[J].Bioinformatics.1998.14(4):349-356
222 Adams MD.Kerlavage AR.Fleischmann RD,et al.Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence [J].Nature(6547 suppl).1995.377:173-174
223 Hwang DM.Fung YW.Wang RX,et al.Analysis of expressed sequence tags from a fetal heart cDNA library[J].Genomics.1995.30:293-298
224 Hwang DM.Dempsey AA.Wang RX,et al.A genome-based resource for molecular cardiovas- -cular medicine:Towards a compendium of cardiovascular genes[J].Circulation.1997. 96:4146-4203
225 Ton C.Hwang DM.Dempsey AA,et al.Identification. characterization. and mapping of expressed sequence tags from an embryonic zebrafish heart cDNA library[J].Genome Res.2000.10:1915-1927
226 Zsurger N.Mazella J.Vincent JP.Solubilization and purification of a high affinity neurotensin receptor from newborn human brain[J].Brain Res.1994.639(2):245-252
227 Mazella J.Zsurger N.Navarro V,et al.The 100KDa neurotensin receptor is gp95/ sortilin,a non-G-protein-coupled receptor[J].J Biol Chem.1998.273(41):26273- 26276
228 Munck PC.Nielsen MS.Jaoobsen C,et al.Propeptide cleavage conditions sortilin/ neurotensin receptor3 for ligand binding[J].EMBO.1999.18(3):595-604
229 Takenaka H.Yasuno H.Kishimoto S.Immunolocalization of fibroblast growth factorreceptors in normal and wounded human skin[J].Arch Dermatol Res.2002.294(7):331- 338
230 Roghani M.Moscatelli D.Prostate cells express two isoforms of fibroblast growth factor receptor 1 with different affinities for fibroblast growth factor 2[J]. Prostate. 2007.67(2):115-124
231 Hacohen N.Kramer S.Sutherl D,et al.Sprouty encodes a novel an tagonist of FGF singaling that patterns apical branching of the Drosophla airways[J].Cell.1998.92: 253-263
232 Ito C.Saitoh Y.Fujita Y,et al.Decapeptide with fibroblast growth factor(FGF)-5 partial sequence inhibits hair growth suppressing activity of FGF5[J].Cell Physiol. 2003. 197(2):272-283
233 Kramer S.Okabe M.Hacohen N,et al.Sprouty:a common antagonist of FGF and EGF signaling pathways in Drosophila[J].Development.1999.126:2515-2525
234王蘅文主编.实用肿瘤学基础[M].北京:人民卫生出版社出版.1992
235李志立.苏业璞.高博.ras基因与肿瘤[J].河北医科大学学报.2001.22(4):240-242
236 Vallee BL.Falchul KH.The biochemical basis of zinc physiology[J].Physiol Rev.1993. 73:79-118
237 Tremble PM.Lane TF.Sage EH,et al.SPARC,a secreted protein associated with morpho- -genesis and tissue remodeling,induces expression of metalloproteinases in fibro- -blasts through a novel extracellular matrix-dependent pathway[J].Cell Biol.1993. 121(6):1433-1444
238 Garrod DR.Desmosomes and hemidesmosomes[J].Curr Opin Cell Biol.1992.5(1):30-40
239 King IA.Sullivan KH.Bennett R,et al.The desmocollins of human foreskin epidermis: identification and chromosomal assignment of third gene and expression patterns of the three isoforms[J].Invest Dermatol.1995.105(3):314-321
240 Hitomi J.Kimura T.Kusumi E,etal.Novel S100 prorteins in human esophageal epithelial cells:CAAFI experssion is associated with cell growth arrest[J].Acrh Histol Cytol. 1998:61(2):163-178
2 Gat U.Dasgupta R.Degenstein L,et al.Hair follicle morphogenesis and hair tumors in mice expressing a truncatedβ-catenin in skin[J].Cell.1998.95(5):605-614
3 Matsuzaki T.Yoshizato K.Role of hair papilla cells on induction and regeneration processes of hair follicles[J].Wound Repair and Regeneration.1998.6(6):524-530
4 Kumamoto T.Shalhevet D.Matsue H,et al.Hair follicles serve as local reservoirs of skin mast cell precursors[J].Blood.2003.102(5):1654-1660
5 Buli JJ.Muller-Rover S.Chronnell CM,et al.Contrasting expression patterns of CCAAT /enhancer-binding protein transcription factors in the hair follicle and at different stages of the hair growth cycle[J].J Invest Dermatol.2002.118(1):17-24
6 Paus R.Muller-R?ver S.Vander VC,et al.Comprehensive guide for the recognition and classification of distinct stage of hair follicle morphogenesis[J].Invest Dermatol. 1999.113(4):523-532
7 Nanba D.Hieda Y,et al.Remodeling of desmosomal and hemidesmosomal adhesion systems during early morphogenesis of mouse pelage hair follicles[J].Invest Dermatol.2000. 114:171-177
8 Hardy MH.The secret life of the hair follicle[J].Trends Genet.1992.8:55-61
9李国强.纪影畅.李宇.毛囊形态发生的分子机制[J].国外医学皮肤性病学分册.2004.30(1):38 -40
10 DasGupta R.Fuchs E.Multiple roles for activated LEF/TCF transcription complexes during hair follicle developmemt and differentiation[J].Development.1999.126:4557- 4568
11 St-Jacques B.DassuLe HR.Karavanova I,et al.Sonic hedgehog signaling is essential for hair development[J].Curr Biol.1998.8:1058-1068
12 Botchkarev VA.Botchkareva NV.Roth W,et al.Noggin is a mesenchymally derived stimulator of hair-follicle induction[J].Nat Cell Biol.1999.1(3):158-164
13 Reddy S.Andl T. Bagasra A,et al.Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis[J].Mech Dev.2001.107:69-82
14 Huelsken J.Vogel R.Erdmann B,et al.β-catenin Drivers hair follicle morphogenesis and stem cell differentiation in the skin[J].Cell.2001.105:533-545
15 Jamora C.DasGupta R.Kocieniewski P,et al.Links between signal transduction,trans- -cription and adhesion in epithelial bud development[J].Nature.2003.422 (6929):317-322
16 Yan MH.Wang LC.Sarah G,et al.Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors[J].Science.2000.290:523- 527
17 Kumar A.Eby M T.Sinha S,et al.The ectodermal dysplasia receptor activates the nuclear factor- B. JNK. and cell death pathways and binds to ectodysplasin A[J].Biol.Chem. 2001.276:2668-2677
18 Foitzik K.Paus R.Doetschman T,et al.The TGFβ2 isoform is both a required and sufficient inducer of murine hair follicle morphogenesis[J].Dev Biol.1999.212:278- 289
19 Massaque J.Chen YC. Driverling TGFβsignaling[J].Genes Dev.2000.14:627-644
20 Du Cros DL.Isaacs K.Moore GP.Localization of epidermal growth factor immunoreac- -tivity in sheep skin during wool follicle development[J].Invest Dermatol.1992.98: 109-115
21 Nanney LB.Magid M.Stoscheck CM,et al. Comparison of epidermal growth factor binding and receptor distribution in normal human epidermis and epidermal appendages[J]. Invest Dermatol.1984.83:385-393
22 Wang LC.Liu ZY.Gambardella L,et al.Regular articles:conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration[J].Invest Dermatol.2000.114(5):901-908
23 Karlsson L.Bondjers C.Betsholtz C.Roles for PDGFA and sonic hedgehog in development of mesenchymal components of the hair follicle[J].Development.1999.126:2611-2621
24 Muller-Rover S.Handjiski B.Vander VC,et al.A comprehensive guide for the accurate classitifacation of murine hair follicles in distinct hair cycle stages[J].Invest Dermatol.2001.117(1):3-15
25 Ryder ML.Hair[M].London:Arnold.1973
26 Argyris TS.The effects of wounds on adjacent growing or resting hair follicles in mice[J].Arch Dermatol Symp.1956.61:31-36
27 Paus R. Muller-Rover S.and Botchkarev VA. Chronobiology of the hair follicle: hunting the“hair cycle clock”[J].Invest Dermatol.1999.4:338-345
28 Stenn KS and Paus R.What Drivers hair follicle cycling[J]?Exp Dermatol.1999.8:229- 236
29 Balsalobre A.Damiola F.Schibler U.A serum shock induces circadian gene expression in mammalian tissue culture cells[J].Cell.1998.93:929-937
30 Hardy MH.Van Exan RJ.Sonstegard KS,et al.Basal lamina changes during tissue interactions in hair follicles-an in vitro study of normal dermal papillae andvitamin A-induced glandular morphogenesis[J].Invest Dermatol.1983.80:27-34
31 Hardy MH.The differentiation of hair follicles and hairs in organ culture[J].Adv Biol Skin.1969.9:35-60
32 Maurer M.Peters EMJ.Botchkarev VA,et al.Intact hair follicle innervation is not essential for growth induction and development[J].Arch Dermatol Res.1998.290:574- 578
33宋志强.郝飞.毛乳头及毛囊生长调控的若干研究进展[J].重庆医学.2003.32(8):1087-1089
34 Stenn KS.Combates NJ.Eilertsen KJ,et al.Hair follicle growth drivers[J].Dermatol Clin.1996.14:543-558
35 Nagorcka BN and Mooney JR.The role of a reaction-diffusion system in the initiation of primary hair follicles[J].Theor Biol.1985.114:243-272
36 Risek B.Klier FG.and Gilula NB.Multiple gap junction genes are utilized during rat skin and hair development[J].Development.1992.116:639-651
37 Stenn KS and Paus R. Drivers of hair follicle cycling[J].Physilogical Reviews.2001. 81:449-494
38 Johnson E and Ebling FJ.The effect of plucking hairs during different phases of the follicuLar cycle[J].Embryol Exp Morphol.1964.12:465-474
39 Paus R.Muller-Rover S.and Mckay I.Driver of the hair follicle growth cycle.In:Hair Biology and Hair Growth Disorders[M].Price V.London:Dunitz.83-94
40 Chase HB.Growth of hair[J].Physiol Rev.1954.34:113-126
41 Argyris TS and Trimble ME.On the mechanism of hair growth stimulation in wound healing [J].Dev Biol.1964.9:230-254
42 Reynolds AJ and Jahoda CAB. Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis[J].Development.1993. 115:587-593
43 Paus R.Stenn KS.and Link RE.Telogen skin contains an inhibitor of hair growth[J].Br Dermatol.1990.122:777-784
44 Cotsarelis G.Sun TT.Link RE.Label-retaining cells reside in the bulge area of pilo- -sebaceous unit:implications for follicular stem cells,hair cycle and skin carino- -genesis[J].Cell.1990.61(7):1329-1337
45 Philpott MP.Paus R.Principles of hair follicle morphogenesis.Chuong CM.editor. Molecular basis of epithelial appendage morphogenesis[M].Landes Bioscience Publications.1998:75-103
46 Stenn K.Parimoo S.Growth of the hair follicle:a cycling and regenerating biological system.Chuong CM.editor.Molecular basis of epithelial appendage morphogenesis [M].Landes Bioscience Publications.1998:111-131
47 Paus R.Cotsarelis G.The biology of hair follicles[J].Med.1999.341:491-498
48 Alexeev V.Igoucheva O.Localized in vivo genotypic and phenotypic correction of the albino mutation in skin by RNA-DNA oligo nucleotide[J].Nature Biotechnol.2000.(18): 43-47
49吕中法.刘荣卿.细胞因子与毛囊生长周期[J].国外医学.生理、病理科学与临床分册.1999.19 (6):491-495
50屠军波.扬壮群.毛囊的体外培养及相关生长因子研究进展[J].中国美容医学.2001.10(4): 354-356
51 Hardy H.费伦奇.山羊[M].1983.1-28
52李金泉.绒山羊绒毛生长调控机理研究进展[J].中国草食动物.2001.21(3):41-43
53白俊艳.贾小平.李金泉.中国绒山羊育种研究进展[J].内蒙古农业科技.2006(2):20-22
54李金泉.内蒙古绒山羊育种原理与方法的研究[D].中国农业大学访问学者研究报告.2000:8-9
55尹俊.内蒙古绒山羊毛囊发育、生长周期及相关基因的研究[D].内蒙古大学.2004
56李长青.绒山羊毛囊周期性变化与生长期毛囊KAP13-1基因的表达[D].内蒙古农业大学.2005
57张燕军.内蒙古绒山羊皮肤毛囊发育规律及Hoxc9基因的研究[D].内蒙古农业大学.2007
58 Russel AJ.Fibre production from sheep and goats[J].The progress of sheep and research.1992.11:235-256
59贾志海.安民.山羊绒生长机理研究进展[J].草食家畜.1996.(1):2-6
60张春兰.内蒙古阿尔巴斯白绒山羊毛囊生长周期性变化与KAP6cDNA的特征分析[D].内蒙古农业大学.2003
61王永.郑玉才.龙虎等.中国山羊业研究[M].成都:四川科学技术出版社.1998:144-164
62 Mcdonald BJ.Hoey WA.Hopkins PS.Effect of photo-translocation on fleece growth in cashmere goats[J].Agric Res.1987.38:765-773
63税世荣.内蒙古绒山羊分布及其绒质绒量与生态条件的关系[J].内蒙古畜牧科学.1994(2):14 -17
64甄玉国.绒山羊生绒机理及其营养研究进展[J].内蒙古畜牧科学.2000.21(4):1-5
65 Johnson TJ.Rowe JB. Growth and cashmere production by goats in relation to dietary protein supply[C].Proceedings of the Australian Society of Animal Production.1984. 15:400-403
66李金泉.尹俊.绒山羊育种研究现状及展望[J].草食家畜.2001.1(3):19-23
67 Adelson DL.Cam GR.Desilva UF.Gene expression in sheep skin and wool(hair)[J]. Genomics.2004.83:95-105
68高爱琴.成纤维细胞生长因子5(FGF5)基因cDNA克隆及在不同品种绵羊和山羊中的多态性研究[D].内蒙古农业大学.2005
69席海燕.尹俊等.Hox基因Prox1在绒山羊皮肤中的表达[C].中国草食动物.2005-2006年全国养羊生产与学术研讨会议论文集.84-86
70赵珺.内蒙古绒山羊与蒙古绵羊BMP-2基因片段的克隆及表达[D].内蒙古农业大学.2006
71刘铮铸.山羊肌肉生长抑制素基因多态性及其与生产性能相关性研究[D].内蒙古农业大学. 2006
72张俊霞.山羊HGT KAP基因家族成员的克隆及其mRNA在皮肤中的表达[D].内蒙古农业大学. 2007
73李荣.内蒙古绒山羊BMP-4、BMPR-IB基因cDNA的克隆及BMPR-IB在皮肤毛囊中的表达[D].内蒙古农业大学.2007
74李玉荣.尹俊.张燕军等.绒山羊胚胎期和生长期皮肤毛囊差异表达基因研究[J].湖北农业科学.2008.47(2):146-148
75裴雪涛.干细胞生物学[M].北京:科学出版社.2003
76周家喜.人类和小鼠表皮干细胞的分离、鉴定和特性研究[D].中国科学院动物研究所.2004
77 Brouard M.Barrandon Y.Driverling skin morphogenesis:hope and despair[J].Curr Opin Biotechnol.2003.14(5):520-525
78 Bickenbach JR.Chism E.Selection and extended growth of murine epidermal stem cells in culture[J].Exp Cell Res.1998.244:184-195
79 Kaur P.Li A.Adhesive properties of human basal epidermal cells:an analysis of keratinocyte stem cells,transit amplifying cells and postmitotic differentiating cells[J].Invest Dermatol.2000.114(3):413-420
80 Jones PH.Isolation and characterization of human epidermal stem cells[J].Clin sci. 1996.91:141-146
81 Cotsarelis G.Kaur P.Dhouailly D,et al.Epithelial stem cells in the skin:definition, markers,localization and functions[J].Exp Dermatol.1999.8:80-88
82 Watt FM.Herde MD.Keratinocyte integrins.The keratinocyte handbook[M].Cambridge University Press.1994.153-164
83 Jones PH.Epithelial stem cells[J].1997.19:683-690
84 Brakebusch C.Richard G.Quondamatteo F,et al.Skin and hair follicle integrity is crucially dependent on integrinβexpression on keratinocytes[J].EMBO.2000.19: 3990-4003
85 Tani H.Morris RJ and Kaur P.Enrichment for murine keratinocyte stem cells based on cell surface phenotype[J].PNAS.2000.97:10960-10965
86 Li A.Simmons PJ.Kaur P.Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype[J].PNAS.1998.95:3902-3907
87 Lyle S.Christofidou SM.Liu Y,et al.The C8/144B monoclonal antibody recognizescytokeratin15 and defines the location of human hair follicle stem cells[J].Cell Sci.1998.111(21):3179-3188
88 Michel M.Torok N.Godbout MJ,et al.Keratin19 as a biochemical marker of skin stem cells in vivo and in vitro:Keratin19 expressing cells are differentially localized in function of anatomic sites,and their number varies with donor age and culture stage[J].Cell Sci.1996.109:1017-1028
89 Michel M. L'Heureux N.Auger FA,et al.From newborn to adult:phenotypic and functional properties of skin equivalent and human skin as a function of donor age[J].Cell Physio.1997.171:179-189
90 Lyle S.Christofidou SM.Liu Y,et al.Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype[J].Invest Dermatol Symp Proc. 1999.4(3):296-301
91 Pellegrini G.Dellambra E.Golisano O,et al.P63 identifies keratinocyte stem cells [J].PNAS.2001.98(6):3156-3161
92 Yang A.Schweitzer R.Sun D,et al.P63 is essential for regenerative proliferation in lumb,craniofacial and epithelial development[J].Nature.1999.398:714-718
93 Trempus CS.Morris RJ.Bortner CD,et al.Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34[J].Invest Dermatol.2003. 120(4):501-511
94 Matic M.Petrov IN.Chen S,et al.Stem cells of the corneal epithelium lack connexins and metabolite transfer capacity[J].Differentiation.1997(61):251-260
95 Ohyama M.Terunuma A.Tock CL,et a1.Characterization and isolation of stem cell enriched human hair follicle bulge cells[J].Clin Invest.2006.116:249-260
96 Scott EV and Ekel TM. Geometric relationships between the matrix of the hair bulb and its dermal papilla in normal and alopecic scalp[J].Invest Dermatol.1958.31:281- 287
97 Reynolds AJ and Jahoda CAB. Hair follicle stem cells? A distinct germinative epidermal cell popuLation is activated in vitro by the presence of hair dermal papilla cells[J]. Cell Sci.1991.99:373-385
98 Kobayashi K.Rochat A.Barrandon Y.Segregation of keratinocyte colony-forming cells in the bulge of the rat virissa[J].PNAS.1993.90(15):7391-7395
99 Rochat A.Kobayashi K.Barrandon Y.Location of stem cells of human hair follicles by clonal analysis[J].Cell.1994.76(6):1063-1073
100 Morris RJ.Potten CS.Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of growth[J].Invest Dermatol.1999.112(4):470-475
101 Taylor G.Lehrer MS.Jensen PJ,et al.Involvement of follicular stem cells in forming not only the follicle but also the epidermis[J].Cell.2000.102:451-461
102 Oshima H.Rochat A.Kedziaet C,et al.Morphogenesis and renewal of hair follicles from adult multipotent stem cells[J].Cell.2001.104(2):233-245
103 Tani H.Morris RJ.type[J].PNAS.2000.97(20):10960-10965
104 Dunnwald M.Tomanek CA.Alexandrunas D,et a1.Isolating a pure population of epidermal stem cells for use in tissue engineering[J].Exp Dermatol.2001.10(1):45-54
105 Schofield R.The relationship between the spleen colony-forming cell and the haemopoietic stem cell[J].Blood Cells.1978.4(1-2):7-25
106 Spradling A.Drummond BD.and Kai T.Stem cells find their niche[J].Nature.2001.414 (6859):98-104
107 Wagers AJ.Weissman IL. Plasticity of adult stem cells[J].Cell.2004.116(5):639-648
108 Lavker RM.Sun TT.Oshima H,et a1.Hair follicle stem cells[J].Investig Dermatol Symp Proc.2003.8(1):28-38
109 Tumbar T.Guasch G.GrecoV,et al.Defining the epithelial stem cell niche in skin[J]. Science.2004.303(5656):359-363
110 Blanpain C.Lowry WE.Geoghegan A,et al.Self-renewal,multipotency and the existence of two cell populations within an epithelial stem cell niche[J].Cell.2004.118(5): 635-648
111 Zhu AJ.Haase I.Watt FM.Signaling viaβ1-integrins and mitogenactivated protein kinase determines human epidermal stem cell fate in vitro[J].PNAS.1999.96:6728- 6733
112 Alonso L and Fuchs E.Stem cells in the skin:waste not,Wnt not[J].Genes Dev.2003. 17:1189
113 Fuchs E.Tumbar T and Guasch G. Socializing with the neighbors: stem cells and their niche[J].Cell.2004.116(6):769-778
114 Raghavan S.Bauer C.Mundschau G.et al.Conditional ablation ofβ1-integrin in skin: severe defects in epidermal proliferation.basement membrane formation and hair follicle invagination[J].Cell Biol.2000.150:1149-1160
115孙晓庆.付小兵.盛志勇.表皮干细胞[J].中华创伤杂志.2000.16(10):635-638
116 Logan CY.Nusse R.The Wnt signaling pathway in development and disease[J].Annu Rev Cell Dev Biol.2004.20:781-810
117 Andl T.Reddy ST.Gaddapara T,et al.WNT signals are required for the initiation of hair follicle development[J].Dev Cell.2002.2(5):643-653
118 Merrill BJ.Gat U.DasGupta R,et al.Tcf3 and Lef1 regulate lineage differentiationof multipotent stem cells in skin[J].Genes Dev.2001.15(13):1688-1705
119 Van MD.Kolligs FT.Dlugosz AA,et al.Transient activation ofβ-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice[J].Genes Dev.2003.17(10):1219-1224
120 Locelso C.Prowse DM.Watt FM.Transient activation ofβ-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours[J].Development.2004.131(8):1787-1799
121 Kanitakis J.Bourchany D.Faure M,et al.Expression of the hair stem cell-specific keratin15 in pilar tumors of the skin[J].Eur Dermatol.1999.9(5):363-365
122 Beaudoin GM.Sisk JM.CouLombe PA,et al.Hairless triggers reactivation of hair growth by promoting Wnt signaling[J].PNAS.2005.102(41):14653-14658
123 Braun KM.Niemann C.Jensen UB,et al.Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in whole mounts of mouse epidermis[J].Development.2003.130(21):5241-5255
124 Blanpain C.Fuchs E.Epidermal stem cells of the skin[J].Annu Rev Cell Dev Biol.2006. 22:339-373
125 Tsakonas SA.Rand MD.Lake RJ.Notch signaling:cell gate driver and signal integration in development[J].Science.1999.284:770-776
126 Lowell S.Jones P.Leroux I,et al. StimuLation of human epidermal differentiation by delta-notch sigalling at the boundaries of stem cell clusters[J].Curr Bio.2000. 10:491-500
127 Gandarillas A.Watt FM.c-Myc promotes differentiation of human epidermal stem cells [J].Genes Dev.1997.11(21):2869-2882
128 Willert K.Brown JD.Danenbrg E,et al.Wnt proteins are lipid-modified and can act as stem cell growth factors[J].Nature.2003.423(6938):448-452
129 Arnold I.Watt FM.c-Myc activation in transgenic mouse epidermis result in mobilization of stem cells and differentiation of their progeny[J].Curr Biol.2001. 11(8):558-568
130 Frye M.Gardner C.Li ER,et al.Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interaction with the local micro- environment[J].Development.2003.130(12):2793-2808
131 Niemann C.Owens DM.HuLsken J,et al.Expression of Delta N-Lef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours[J].Development.2002.129(1):95-109
132 Jamora C.Fuchs E.Intercellular adhesion.signaling and the cytoskeleton [J].Nat CellBiol.2002.4(4):E101-108
133 Honeycutt KA.Roop DR.c-Myc and epidermal stem cell fate determination[J]. Dermatol.2004.31(5):368-375
134 Fuchs E.Scratching the surface of skin development[J].Nature.2007.445(7130): 834-842
135 Zhang JW.He XC.Tong WG,et al.Bone morphogenetic protein signaling inhibits hair follicle growth induction by restricting epithelial stem/progenitor cell activation and expansion.Stem Cells[J].2006.24(12):2826-2839
136 Moore KA.Lemischka IR.Stem cells and their niches[J].Science.2006.311(5769):1880- 1885
137 Hashimoto A.Kurosaki M.Gotoh N.Shc regulates epidermal growth factor-induced activation of the JNK signaling pathway[J].Biol Chem.1999.274:20139-20143
138 Haase I.Evans R.Pofahl R,et al.Regulation of keratinocyte shape. migration and wound epithelialization by IGF1- and EGF-dependent signaling pathways[J].Cell Sci.2003. 116:3227-3238
139 Mann A.Breuhahn K.Schirmacher P,et al.Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing:stimulation of keratinocyte proliferation,granulation tissue formation and vascularization[J].Invest Derm. 2001.117:1382-1390
140 Ferrari G.Cusella G.Angelis D,et al. Muscle regeneration by bone marrow-derived myogenic progenitors[J].Science.1998.279:1528-1530
141 Brazelton TR.Rossi FMV.Keshte GI,et al.From marrow to brain:expression of neuronal phenotypes in adult mice[J].Science.2000.290:1775-1779
142 Krause DS.Theise ND.Collector MI,et al.Multi-organ,multi-lineage engraftement by a single bone marrow-derived stem cell[J].Cell.2001.105:369-377
143 Lagasse E.Connors H.Dhalimy MAl,et al.Purified hematopoietic stem cells can differentiate into hepatocytes in vivo[J].Nature Medicine.2000.6(11):1229-1234
144 Anderson DJ.Gage FH.Weissman IL.Can stem cells cross lineage boundaries?[J].Nat Med.2001.7(4):393-395
145 Bjornson CR.Rietze R L.ReynoldsB A,et al.Turning brain into blood:a hematopoietic fatead opted by adult neural stem cells in vivo[J].Science.1999.283:534-537
146 Sata M.Saiura A.Kunisato A,et al.Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis[J].Nature Medicine.2002.8(4):403-409
147 Liang L.Bickenbach JR.Somatic epidermal stem cells can produce multiple cell lineagesduring development[J].Stem cells.2002.20:21-31
148 Toma J G.Akhavan M.Fernandes JL.Isolation of multipotent aduLt stem cells from the dermis of mammalial skin[J].Nature Cell Biology.2001.3:778-784
149 Lako M.Armstrong L.Cairns PM,et al.Hair follicle dermal cells repopulate the mouse heamatopoietic system[J].Cell Sci.2002.115:3967-3974
150史春梦.真皮来源成体多能干细胞的生物学性状与促进创伤修复的实验研究[D].第三军医大学.2003
151杨学义.表皮干细胞建系及重建角膜缘干细胞缺损眼表研究[D].西北农林科技大学.2004
152史明艳.山羊毛囊干细胞及组织工程皮肤构建研究[D].西北农林科技大学.2006
153刘迎春.成年绒山羊皮肤干细胞的分离、纯化、鉴定与诱导[D].内蒙古农业大学.2007
154 Saiful Islam.MD.Isolation.Characterization and directional differentiation of skin stem cells derived from cashmere goat fetus[D].内蒙古农业大学.2007
155付小兵.方利君.王玉新等.骨髓间充质干细胞自体移植提高猪皮肤创面修复质量的初步研究[J].中华医学杂志.2004.84(11):920-923
156 Brouard M.Barrandon Y.Driverling skin morphogenesis:hope and despair[J].Current Opinion Biotechnol.2003.14(5):520-525
157 Kuhn U.Terunuma A.Pfutzner W,et al.In vivo assessment of gene delivery to keratinocytes by lentiviral vectors[J].J Virol.2002.76(3):1496-1504
158高艳红.裴雪涛.皮肤干细胞的研究现状与应用前景[J].中华烧伤杂志.2003.19(1):60-62
159 Lee SW.Tomasetto C and Sagar R.Positive selection of cadidate tumor-suppresser genes by subtractive hybridization[J].PNAS.1991.88:2825-2829
160 Liang P and Pardee AB.Differential display of eukaryotic messenger RNA by means of the Polymerase Chain Reaction[J].Science.1992.257(14):967-971
161 Shoham NG.Arad T.Rosin AR,et al.Differential display assay and analysis[J]. Biotechniques.1996.20(2):182-184
162 Zegzouti H.Jones B.Marty C,et al.Improved screening of cDNAs generated by mRNA differential display enables the selection of true positives and the isolation of weekly expressed messages[J].Plant Molecular Biology.1997.15:236-245
163 Lisitsyn N and Wigler M.Cloning the differences between two complex genomes[J]. Science.1993.259(5907):946-951
164 Diatchenko L.ChrisLau YF.Campbell AP,et al.Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries[J].PNAS.1996.93(12):6025-6030
165 Velculescu VE.Zhang L.Vogelstein B,et al.Serial analysis of gene expression[J]. 1995.270(5235):484-487
166 Richards M.Tan SP.Tan JH.The transcriptome profile of human embryonic stem cells as defined by SAGE[J].Stem Cells.2004.22(1):51-64
167 Quere R.Manchon L.Lejeune M,et al.Mining SAGE data allows large-scale,sensitive screening of antisense transcript expression[J].Nucleic Acids Res.2004.32.(20): e163(1-7)
168 Keime C.Damiola F.Mouchiroud D,et al.Identitag,a relational database for SAGE tag identification and interspecies comparison of SAGE libraries[J].BMC Bio informatics. 2004.5:143(1-12)
169 Boheler KR.Tarasov KV.SAGE analysis to identify embryonic stem cell-predominant transcripts[J].Methods Mol Biol.2006.329:195-221
170 Richards M.Tan SP.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[J].Stem Cells.2006.24(5):1162-1173
171 Kurian KM.Watson CJ and Wyllie AH.DNA chip technology[J].Pathol.1999.187(3):267- 271
172 Sheets MD.Amersdorfer P.Finnern R,et al.Efficient construction of a large nonimmune phage antibody liberary:The production of high-affinity human single-chain antibodies to protein antigens[J].PNAS.1998.95(11):6157-6162
173 Burioni R.Plaisant P.Bugli F,et al.A new subtraction technique for molecular clonging of rare antibody specifities from phage display libraries[J].Res.Virol.1998.149(5): 327-330
174 Guy GR.Philip R and Tan YH. Analysis of cellular phosphoproteins by two-dimensional gel electrophoresis:Applications for cell signaling in normal and cancer cells[J]. Elecophoresis.1994.15(3-4):417-440
175欧阳曙光.贺福初.生物信息学:生物实验数据和计算技术结合的新领域[J].科学通报.1994.44:1457-1468
176张春霆.生物信息学的现状与展望[J].世界科技研究与发展2000.(6):17-20
177 Rudert FG.Ilag L.Functional genomicswith protein-protein interactions[J].Biotech- nol.Annul.Rev.2000.(5):45-86
178 Samuel A.Jarrod C.Elia S,et al.Whole-genome shotgun assembly and analysis of the genome of Fugu rubripes[J].Science.2002.(297):1301-1310
179胡志远.贺福初.蛋白质组研究进展[J].生物化学与生物物理进展.1999.(3):202-204
180尹文兵.黄勤妮.印莉萍.模式植物蛋白质组研究进展[J].生物信息学.2004.(2):47-50
181 Gierke P.Zhao C.Brackmann M.Expression analysis of members of the neuronal calciumsensor protein family:combining bioinformatics and western blot analysis[J]. Biochemical and Biophysical Research Communications.2004.(1):38-43
182王亚辉.世纪之交生物学发展的主要趋势[J].中国科学基金.2000.(3):167-168
183 Eric J.Current trends in bioinformatics[J].Trends in Biotechnology.2002.20(8): 317-319
184芮菊生.杜懋芩.陈海明等.组织切片技术[M].北京:人民卫生出版社.1980
185 Nixon AJ.A method for determining the activity state of hair follicles[J].Biotech Histochem.1993:68(6):316-325
186王伯沄.李玉松.黄高升等.病理学技术[M].北京:人民卫生出版社.2000
187安伟.内蒙古绒山羊毛囊的分离培养和类初级毛囊干细胞的分离及培养[D].内蒙古农业大学.2007
188黄文孝.肖红俊.汪吉宝等.用BrdU标记技术观察大鼠内淋巴囊的S期细胞[J].中国组织化学与细胞化学杂志.2002.11(4):4003
189 Gratzner HG. Monoclonal antibody to 5-bromo and 5-iododeoxyuridine:a new reagent for detection of DNA replication[J].Science.1982.218(4571):474-475
190 Nakamura S.Takeda Y.Kanno M,et al. Application of BrdU and anti-BrdU monoclonal antibody for the in vivo analysis of proliferative characteristics of human leukemia cells in bone marrow[J].Oncology.1991.48(4):285-289
191陈广平.郭慕依.陈琦等.应用BrdU单抗免疫组化染色观察大鼠系膜细胞生长情况[J].上海医科大学学报.1996.23(4):305-306
192 Xiang ZZ and Markel MD.Bromodeoxyuridine immunohistochemistry of epon-embedded undecalcified bone in a canine fracture healing model[J].Histochem Cytochem.1995. 43(6):629-635
193 Pollack A.Terry NH.Wu CS,et al.Specific staining of iododeoxyuridine and bromo- -deoxyuridine in tumors double labelled in vivo:a cell kinetic analysis[J]. Cytometry. 1995.20(1):53-61
194刘华庆.欧阳旭红.免疫组化的标准化[J].贵州医药.2001.25(8):754-755
195李甘地主编.组织病理技术[M].北京:人民卫生出版社.2002.43-47
196成娘.刘卫平.李甘地.用EDTA缓冲液做抗原修复增强ER.PR免疫组化染色[J].临床与实验病理学杂志.2001.17(3):274
197 Philpott MP.Green MR.Kealey T.Human hair growth in vitro[J].Cell Sci.1990.97:463- 471
198 Green MR.Clay CS.Gibson WT,et al.Rapid isolation in large numbers of intact,viable, individual hair follicles from skin:biochemical and ultrastructural characteri- -zation[J].Invest Dermatol.1986.87:768-770
199 Rogers G.Martinet N.Steinert P,et al.Cultivation of murine hair follicles as organoids in a collagen matrix[J].Invest Dermatol.1987.89:369-379
200 Misago N.Toda S.Sugihara H,et al.Proliferation and differentiation organoid hair follicle cells co-cultured with fat cells in collagen gel matrix culture[J].Br J Dermatol.1998.139(1):40-48
201武津津.刘荣卿.叶庆佾等.毛乳头细胞高效分离培养方法探索[J].中华皮肤科杂志.1997.30 (6):383-385
202程波.刘荣卿.武津津等.改良毛乳头细胞培养法[J].中华皮肤科杂志.2001.34(5):387-388
203 Ibraheem M.Galbratth H.Scaife J,et al.Growth and viability of secondary hair follicles of the Angora goat cultured in vitro[J].Anat.1993.182:231-238
204 Ibraheem M.Galbratth H.Scaife J.et al.Growth of secondary hair follicles of the Cashmere goat in vitro and their response to prolactin and melatonin[J]. Anat.1994. 185:135-142
205陈阅增主编.普通生物学[M].北京:高等教育出版社.1997
206 Parsa R.Yang A.McKeon F,et al.Association of P63 with proliferative potential in normal and neoplastic human keratinocytes[J].Invest Dermatol.1999.113(6):1099- 1105
207 L Li and T Xie.Stem cell niche:structure and function[J]. Annu Rev Cell Dev Biol. 2005. 21:605-631
208 Rizvi AZ and Wong MH.Epithelial stem cells and their niche:There’s no place like home.Stem Cells.2005.23:150-165
209 J.萨姆布鲁克.D.W.拉塞尔著.黄培堂等译.分子克隆实验指南[M].(第三版)北京:科学出版社.2002
210 Chenchik A.Zhu YY.Diatchenko L,et al.Generation and use of high-quality cDNA from small amounts of total RNA by SMART.In Gene Cloning and Analysis by RT- PCR(Bio Techniques Boods.MA)PP.305-319
211 Zhumabayeva B.Diatehenko L.Chenehik A,et a1.Use of SMARTTM generated cDNA for gene expression studies in multiple human tumors[J].Biotechniques.2001.30(1):158-163
212 Kuang WW.Thompson DA.Hoch RV,et al.Differential screening and suppression subtrac- -tive hybridization identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line[J].Nucleic Acids Res.1998.26(4):1116- 1123
213 Yang GP.Ross DT.Kuang WW,et al.Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes[J].Nucleic Acids Res.1999.27(6): 1517-1523
214 Girard JP.Baekkevold ES.Takeshi Yamanaka.et al.Heterogeneity of endothelial cells: The specialized phenotype of human high endothelial venules characterized by suppression subtractive hybridization[J].Am J Pathol.1999.155(6):2043-2055
215 Von SO.Thies WG.and Hofmann M.A high throughput screening for rarely transcribed differentially expressed genes[J].Nucleic Acids Res.1997.25:2598-2602
216张红缨.张今.PCR技术应用的新进展[J].生物化学与生物物理进展.1996.23(6):509-513
217 Clark JM.Novel nontemplated nucleotide addition reactions catalyzed by procaryotic and eucaryotic DNA polymerase[J].Nucl Acids Res.1988.16(20):9677-9686
218 Holton TA.Graham MW.A simple and efficient method for direct cloning of PCR products using ddT-Tailed vectors[J].Nucleic Acids Res.1991.19:1156-1158
219 Huang XQ.Madan A.CAP3:A DNA sequence assembly program[J].Genome Research.1999.9(9): 868-877
220 Newman T.Bruijn FJD.Green P,et al.Genes galore:Asummary of methods for accessing results from large-scale partial sequencing of anonymous arabidopsis cDNA clones [J].Plant Physiology.1994.106(4):1241-1255
221 Anderson I.Brass A.Searching DNA database for similarities to DNA sequenses:when is a match significant?[J].Bioinformatics.1998.14(4):349-356
222 Adams MD.Kerlavage AR.Fleischmann RD,et al.Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence [J].Nature(6547 suppl).1995.377:173-174
223 Hwang DM.Fung YW.Wang RX,et al.Analysis of expressed sequence tags from a fetal heart cDNA library[J].Genomics.1995.30:293-298
224 Hwang DM.Dempsey AA.Wang RX,et al.A genome-based resource for molecular cardiovas- -cular medicine:Towards a compendium of cardiovascular genes[J].Circulation.1997. 96:4146-4203
225 Ton C.Hwang DM.Dempsey AA,et al.Identification. characterization. and mapping of expressed sequence tags from an embryonic zebrafish heart cDNA library[J].Genome Res.2000.10:1915-1927
226 Zsurger N.Mazella J.Vincent JP.Solubilization and purification of a high affinity neurotensin receptor from newborn human brain[J].Brain Res.1994.639(2):245-252
227 Mazella J.Zsurger N.Navarro V,et al.The 100KDa neurotensin receptor is gp95/ sortilin,a non-G-protein-coupled receptor[J].J Biol Chem.1998.273(41):26273- 26276
228 Munck PC.Nielsen MS.Jaoobsen C,et al.Propeptide cleavage conditions sortilin/ neurotensin receptor3 for ligand binding[J].EMBO.1999.18(3):595-604
229 Takenaka H.Yasuno H.Kishimoto S.Immunolocalization of fibroblast growth factorreceptors in normal and wounded human skin[J].Arch Dermatol Res.2002.294(7):331- 338
230 Roghani M.Moscatelli D.Prostate cells express two isoforms of fibroblast growth factor receptor 1 with different affinities for fibroblast growth factor 2[J]. Prostate. 2007.67(2):115-124
231 Hacohen N.Kramer S.Sutherl D,et al.Sprouty encodes a novel an tagonist of FGF singaling that patterns apical branching of the Drosophla airways[J].Cell.1998.92: 253-263
232 Ito C.Saitoh Y.Fujita Y,et al.Decapeptide with fibroblast growth factor(FGF)-5 partial sequence inhibits hair growth suppressing activity of FGF5[J].Cell Physiol. 2003. 197(2):272-283
233 Kramer S.Okabe M.Hacohen N,et al.Sprouty:a common antagonist of FGF and EGF signaling pathways in Drosophila[J].Development.1999.126:2515-2525
234王蘅文主编.实用肿瘤学基础[M].北京:人民卫生出版社出版.1992
235李志立.苏业璞.高博.ras基因与肿瘤[J].河北医科大学学报.2001.22(4):240-242
236 Vallee BL.Falchul KH.The biochemical basis of zinc physiology[J].Physiol Rev.1993. 73:79-118
237 Tremble PM.Lane TF.Sage EH,et al.SPARC,a secreted protein associated with morpho- -genesis and tissue remodeling,induces expression of metalloproteinases in fibro- -blasts through a novel extracellular matrix-dependent pathway[J].Cell Biol.1993. 121(6):1433-1444
238 Garrod DR.Desmosomes and hemidesmosomes[J].Curr Opin Cell Biol.1992.5(1):30-40
239 King IA.Sullivan KH.Bennett R,et al.The desmocollins of human foreskin epidermis: identification and chromosomal assignment of third gene and expression patterns of the three isoforms[J].Invest Dermatol.1995.105(3):314-321
240 Hitomi J.Kimura T.Kusumi E,etal.Novel S100 prorteins in human esophageal epithelial cells:CAAFI experssion is associated with cell growth arrest[J].Acrh Histol Cytol. 1998:61(2):163-178