SALL4 maintains self-renewal of porcine pluripotent stem cells through downregulation of OTX2
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摘要
Sall4 as one of the spalt family members contains several alternative splicing variants, which are differentially expressed and has a key role in maintaining pluripotent stem cells. However, the molecular features and function of SALL4 have not been well elucidated in porcine induced pluripotent stem cells(piPSCs). In this study, we identi?ed SALL4 splice variants and found two SALL4 splicing variants through analysis of the porcine transcriptome data derived from piPSCs. SALL4 A was only detected in piPSCs but SALL4 B was globally expressed in porcine tissues and piPSCs. The level of SALL4 B was signi?cantly reduced when piPSCs differentiation occurred, however, the expression of SALL4 A was not affected, indicating that SALL4 B may be essential for the maintenance of piPSCs self-renewal. Overexpression of SALL4 A and SALL4 B in PEF cells could signi?cantly stimulated expression of endogenous pluripotent genes,when SALL4 B signi?cantly promoted OCT4 expression.Conversely, SALL4 A signi?cantly promoted KLF4 expression. Additionally, both SALL4 A and SALL4 B could repress OTX2 promoter activity in a dose-dependent manner. Conversely, OTX2 also negatively regulated SALL4 expression. These observations indicate that a negative feedback regulatory mechanism may exist between SALL4 and OTX2, which is useful for the maintenance of the self-renewal of piPSCs.
Sall4 as one of the spalt family members contains several alternative splicing variants, which are differentially expressed and has a key role in maintaining pluripotent stem cells. However, the molecular features and function of SALL4 have not been well elucidated in porcine induced pluripotent stem cells(piPSCs). In this study, we identi?ed SALL4 splice variants and found two SALL4 splicing variants through analysis of the porcine transcriptome data derived from piPSCs. SALL4 A was only detected in piPSCs but SALL4 B was globally expressed in porcine tissues and piPSCs. The level of SALL4 B was signi?cantly reduced when piPSCs differentiation occurred, however, the expression of SALL4 A was not affected, indicating that SALL4 B may be essential for the maintenance of piPSCs self-renewal. Overexpression of SALL4 A and SALL4 B in PEF cells could signi?cantly stimulated expression of endogenous pluripotent genes,when SALL4 B signi?cantly promoted OCT4 expression.Conversely, SALL4 A signi?cantly promoted KLF4 expression. Additionally, both SALL4 A and SALL4 B could repress OTX2 promoter activity in a dose-dependent manner. Conversely, OTX2 also negatively regulated SALL4 expression. These observations indicate that a negative feedback regulatory mechanism may exist between SALL4 and OTX2, which is useful for the maintenance of the self-renewal of piPSCs.
Sall4 as one of the spalt family members contains several alternative splicing variants, which are differentially expressed and has a key role in maintaining pluripotent stem cells. However, the molecular features and function of SALL4 have not been well elucidated in porcine induced pluripotent stem cells(piPSCs). In this study, we identi?ed SALL4 splice variants and found two SALL4 splicing variants through analysis of the porcine transcriptome data derived from piPSCs. SALL4 A was only detected in piPSCs but SALL4 B was globally expressed in porcine tissues and piPSCs. The level of SALL4 B was signi?cantly reduced when piPSCs differentiation occurred, however, the expression of SALL4 A was not affected, indicating that SALL4 B may be essential for the maintenance of piPSCs self-renewal. Overexpression of SALL4 A and SALL4 B in PEF cells could signi?cantly stimulated expression of endogenous pluripotent genes,when SALL4 B signi?cantly promoted OCT4 expression.Conversely, SALL4 A signi?cantly promoted KLF4 expression. Additionally, both SALL4 A and SALL4 B could repress OTX2 promoter activity in a dose-dependent manner. Conversely, OTX2 also negatively regulated SALL4 expression. These observations indicate that a negative feedback regulatory mechanism may exist between SALL4 and OTX2, which is useful for the maintenance of the self-renewal of piPSCs.
引文
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2.Ezashi T,Telugu B P V L,Alexenko A P,Sachdev S,Sinha S,Roberts R M.Derivation of induced pluripotent stem cells from pig somatic cells.Proceedings of the National Academy of Sciences of the United States of America,2009,106(27):10993-10998
3.Wu Z,Chen J,Ren J,Bao L,Liao J,Cui C,Rao L,Li H,Gu Y,Dai H,Zhu H,Teng X,Cheng L,Xiao L.Generation of pig induced pluripotent stem cells with a drug-inducible system.Journal of Molecular Cell Biology,2009,1(1):46-54
4.Cheng D,Guo Y,Li Z,Liu Y,Gao X,Gao Y,Cheng X,Hu J,Wang H.Porcine induced pluripotent stem cells require LIF and maintain their developmental potential in early stage of embryos.PLo S One,2012,7(12):e51778
5.Fujishiro S H,Nakano K,Mizukami Y,Azami T,Arai Y,Matsunari H,Ishino R,Nishimura T,Watanabe M,Abe T,Furukawa Y,Umeyama K,Yamanaka S,Ema M,Nagashima H,Hanazono Y.Generation of naive-like porcine-induced pluripotent stem cells capable of contributing to embryonic and fetal development.Stem Cells and Development,2013,22(3):473-482
6.Loh Y H,Wu Q,Chew J L,Vega V B,Zhang W,Chen X,Bourque G,George J,Leong B,Liu J,Wong K Y,Sung K W,Lee C W,Zhao X D,Chiu K P,Lipovich L,Kuznetsov V A,Robson P,Stanton LW,Wei C L,Ruan Y,Lim B,Ng H H.The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.Nature Genetics,2006,38(4):431-440
7.Tan M H,Au K F,Leong D E,Foygel K,Wong W H,Yao M W M.An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.Molecular Systems Biology,2013,9(1):632
8.Elling U,Klasen C,Eisenberger T,Anlag K,Treier M.Murine inner cell mass-derived lineages depend on Sall4 function.Proceedings of the National Academy of Sciences of the United States of America,2006,103(44):16319-16324
9.Yang J,Corsello T R,Ma Y.Stem cell gene SALL4 suppresses transcription through recruitment of DNA methyltransferases.Journal of Biological Chemistry,2012,287(3):1996-2005
10.Yang J,Gao C,Chai L,Ma Y.A novel SALL4/OCT4 transcriptional feedback network for pluripotency of embryonic stem cells.PLo SOne,2010,5(5):e10766
11.Yang J,Chai L,Fowles T C,Alipio Z,Xu D,Fink L M,Ward D C,Ma Y.Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America,2008,105(50):19756-19761
12.Lim C Y,Tam W L,Zhang J,Ang H S,Jia H,Lipovich L,Ng H H,Wei C L,Sung W K,Robson P,Yang H,Lim B.Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages.Cell Stem Cell,2008,3(5):543-554
13.Tatetsu H,Kong N R,Chong G,Amabile G,Tenen D G,Chai L.SALL4,the missing link between stem cells,development and cancer.Gene,2016,584(2):111-119
14.Chen X,Xu H,Yuan P,Fang F,Huss M,Vega V B,Wong E,Orlov Y L,Zhang W,Jiang J,Loh Y H,Yeo H C,Yeo Z X,Narang V,Govindarajan K R,Leong B,Shahab A,Ruan Y,Bourque G,Sung W K,Clarke N D,Wei C L,Ng H H.Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Cell,2008,133(6):1106-1117
15.Wu Q,Chen X,Zhang J,Loh Y H,Low T Y,Zhang W,Zhang W,Sze S K,Lim B,Ng H H.Sall4 interacts with Nanog and cooccupies Nanog genomic sites in embryonic stem cells.Journal of Biological Chemistry,2006,281(34):24090-24094
16.Zhang J,Tam W L,Tong G Q,Wu Q,Chan H Y,Soh B S,Lou Y,Yang J,Ma Y,Chai L,Ng H H,Lufkin T,Robson P,Lim B.Sall4modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1.Nature Cell Biology,2006,8(10):1114-1123
17.Buganim Y,Markoulaki S,van Wietmarschen N,Hoke H,Wu T,Ganz K,Akhtar-Zaidi B,He Y,Abraham B J,Porubsky D,Kulenkampff E,Faddah D A,Shi L,Gao Q,Sarkar S,Cohen M,Goldmann J,Nery J R,Schultz M D,Ecker J R,Xiao A,Young R A,Lansdorp P M,Jaenisch R.The developmental potential of i PSCs is greatly influenced by reprogramming factor selection.Cell Stem Cell,2014,15(3):295-309
18.Nichols J,Zevnik B,Anastassiadis K,Niwa H,Klewe-Nebenius D,Chambers I,Sch?ler H,Smith A.Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.Cell,1998,95(3):379-391
19.West F D,Terlouw S L,Kwon D J,Mumaw J L,Dhara S K,Hasneen K,Dobrinsky J R,Stice S L.Porcine induced pluripotent stem cells produce chimeric offspring.Stem Cells and Development,2010,19(8):1211-1220
20.Yang F,Zhang J,Liu Y,Cheng D,Wang H.Structure and functional evaluation of porcine NANOG that is a single-exon gene and has two pseudogenes.International Journal of Biochemistry&Cell Biology,2015,59:142-152
21.Yang F,Ren Y,Li H,Wang H.ESRRB plays a crucial role in the promotion of porcine cell reprograming.Journal of Cellular Physiology,2018,233(2):1601-1611
22.Wang N,Wang Y,Xie Y,Wang H.OTX2 impedes self-renewal of porcine i PS cells through downregulation of NANOG expression.Cell Death and Discovery,2016,2:16090
23.Chen C,Ai H,Ren J,Li W,Li P,Qiao R,Ouyang J,Yang M,Ma J,Huang L.A global view of porcine transcriptome in three tissues from a full-sib pair with extreme phenotypes in growth and fat deposition by paired-end RNA sequencing.BMC Genomics,2011,12(1):448
24.Xiao S,Xie D,Cao X,Yu P,Xing X,Chen C C,Musselman M,Xie M,West F D,Lewin H A,Wang T,Zhong S.Comparative epigenomic annotation of regulatory DNA.Cell,2012,149(6):1381-1392
25.Langmead B,Trapnell C,Pop M,Salzberg S L.Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.Genome Biology,2009,10(3):R25
26.Ma Y,Cui W,Yang J,Qu J,Di C,Amin H M,Lai R,Ritz J,Krause D S,Chai L.SALL4,a novel oncogene,is constitutively expressed in human acute myeloid leukemia(AML)and induces AML in transgenic mice.Blood,2006,108(8):2726-2735
27.Xu K,Chen X,Yang H,Xu Y,He Y,Wang C,Huang H,Liu B,Liu W,Li J,Kou X,Zhao Y,Zhao K,Zhang L,Hou Z,Wang H,Wang H,Li J,Fan H,Wang F,Gao Y,Zhang Y,Chen J,Gao S.Maternal Sall4 Is indispensable for epigenetic maturation of mouse oocytes.Journal of Biological Chemistry,2017,292(5):1798-1807
28.Zhang S,Guo Y,Cui Y,Liu Y,Yu T,Wang H.Generation of intermediate porcine i PS cells under culture condition favorable for mesenchymal-to-epithelial transition.Stem Cell Reviews and Reports,2015,11(1):24-38
29.Larsen K B,Lutterodt M,Rath M F,M?ller M.Expression of the homeobox genes PAX6,OTX2,and OTX1 in the early human fetal retina.International Journal of Developmental Neuroscience,2009,27(5):485-492
30.Simeone A,Acampora D,Mallamaci A,Stornaiuolo A,D’Apice MR,Nigro V,Boncinelli E.A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo.EMBO Journal,1993,12(7):2735-2747
31.Diaczok D,Romero C,Zunich J,Marshall I,Radovick S.A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.Journal of Clinical Endocrinology and Metabolism,2008,93(11):4351-4359
32.Asadi M H,Khalifeh K,Mowla S J.OCT4 spliced variants are highly expressed in brain cancer tissues and inhibition of OCT4B1causes G2/M arrest in brain cancer cells.Journal of NeuroOncology,2016,130(3):455-463
33.Hwang J Y,Oh J N,Lee D K,Choi K H,Park C H,Lee C K.Identification and differential expression patterns of porcine OCT4variants.Reproduction,2015,149(1):55-66
34.Li D,Yang Z K,Bu J Y,Xu C Y,Sun H,Tang J B,Lin P,Cheng W,Huang N,Cui R J,Yu X G,Zheng X L.OCT4B modulates OCT4Aexpression as ce RNA in tumor cells.Oncology Reports,2015,33(5):2622-2630
35.Tan M H,Au K F,Leong D E,Foygel K,Wong W H,Yao M W.An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.Molecular Systems Biology,2013,9(1):632
36.Boyer L A,Lee T I,Cole M F,Johnstone S E,Levine S S,Zucker JP,Guenther M G,Kumar R M,Murray H L,Jenner R G,Gifford DK,Melton D A,Jaenisch R,Young R A.Core transcriptional regulatory circuitry in human embryonic stem cells.Cell,2005,122(6):947-956
37.Chen X,Xu H,Yuan P,Fang F,Huss M,Vega V B,Wong E,Orlov Y L,Zhang W,Jiang J,Loh Y H,Yeo H C,Yeo Z X,Narang V,Govindarajan K R,Leong B,Shahab A,Ruan Y,Bourque G,Sung W K,Clarke N D,Wei C L,Ng H H.Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Cell,2008,133(6):1106-1117
38.Lim C Y,Tam W L,Zhang J,Ang H S,Jia H,Lipovich L,Ng H H,Wei C L,Sung W K,Robson P,Yang H,Lim B.Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages.Cell Stem Cell,2008,3(5):543-554
39.
40.Rao S,Zhen S,Roumiantsev S,Mc Donald L T,Yuan G C,Orkin SH.Differential roles of Sall4 isoforms in embryonic stem cell pluripotency.Molecular and Cellular Biology,2010,30(22):5364-5380
41.Acampora D,Di Giovannantonio L G,Simeone A.Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition.Development,2013,140(1):43-55
42.Buecker C,Srinivasan R,Wu Z,Calo E,Acampora D,Faial T,Simeone A,Tan M,Swigut T,Wysocka J.Reorganization of enhancer patterns in transition from naive to primed pluripotency.Cell Stem Cell,2014,14(6):838-853
43.Yang S H,Kalkan T,Morissroe C,Marks H,Stunnenberg H,Smith A,Sharrocks A D.Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency.Cell Reports,2014,7(6):1968-1981
2.Ezashi T,Telugu B P V L,Alexenko A P,Sachdev S,Sinha S,Roberts R M.Derivation of induced pluripotent stem cells from pig somatic cells.Proceedings of the National Academy of Sciences of the United States of America,2009,106(27):10993-10998
3.Wu Z,Chen J,Ren J,Bao L,Liao J,Cui C,Rao L,Li H,Gu Y,Dai H,Zhu H,Teng X,Cheng L,Xiao L.Generation of pig induced pluripotent stem cells with a drug-inducible system.Journal of Molecular Cell Biology,2009,1(1):46-54
4.Cheng D,Guo Y,Li Z,Liu Y,Gao X,Gao Y,Cheng X,Hu J,Wang H.Porcine induced pluripotent stem cells require LIF and maintain their developmental potential in early stage of embryos.PLo S One,2012,7(12):e51778
5.Fujishiro S H,Nakano K,Mizukami Y,Azami T,Arai Y,Matsunari H,Ishino R,Nishimura T,Watanabe M,Abe T,Furukawa Y,Umeyama K,Yamanaka S,Ema M,Nagashima H,Hanazono Y.Generation of naive-like porcine-induced pluripotent stem cells capable of contributing to embryonic and fetal development.Stem Cells and Development,2013,22(3):473-482
6.Loh Y H,Wu Q,Chew J L,Vega V B,Zhang W,Chen X,Bourque G,George J,Leong B,Liu J,Wong K Y,Sung K W,Lee C W,Zhao X D,Chiu K P,Lipovich L,Kuznetsov V A,Robson P,Stanton LW,Wei C L,Ruan Y,Lim B,Ng H H.The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.Nature Genetics,2006,38(4):431-440
7.Tan M H,Au K F,Leong D E,Foygel K,Wong W H,Yao M W M.An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.Molecular Systems Biology,2013,9(1):632
8.Elling U,Klasen C,Eisenberger T,Anlag K,Treier M.Murine inner cell mass-derived lineages depend on Sall4 function.Proceedings of the National Academy of Sciences of the United States of America,2006,103(44):16319-16324
9.Yang J,Corsello T R,Ma Y.Stem cell gene SALL4 suppresses transcription through recruitment of DNA methyltransferases.Journal of Biological Chemistry,2012,287(3):1996-2005
10.Yang J,Gao C,Chai L,Ma Y.A novel SALL4/OCT4 transcriptional feedback network for pluripotency of embryonic stem cells.PLo SOne,2010,5(5):e10766
11.Yang J,Chai L,Fowles T C,Alipio Z,Xu D,Fink L M,Ward D C,Ma Y.Genome-wide analysis reveals Sall4 to be a major regulator of pluripotency in murine-embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America,2008,105(50):19756-19761
12.Lim C Y,Tam W L,Zhang J,Ang H S,Jia H,Lipovich L,Ng H H,Wei C L,Sung W K,Robson P,Yang H,Lim B.Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages.Cell Stem Cell,2008,3(5):543-554
13.Tatetsu H,Kong N R,Chong G,Amabile G,Tenen D G,Chai L.SALL4,the missing link between stem cells,development and cancer.Gene,2016,584(2):111-119
14.Chen X,Xu H,Yuan P,Fang F,Huss M,Vega V B,Wong E,Orlov Y L,Zhang W,Jiang J,Loh Y H,Yeo H C,Yeo Z X,Narang V,Govindarajan K R,Leong B,Shahab A,Ruan Y,Bourque G,Sung W K,Clarke N D,Wei C L,Ng H H.Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Cell,2008,133(6):1106-1117
15.Wu Q,Chen X,Zhang J,Loh Y H,Low T Y,Zhang W,Zhang W,Sze S K,Lim B,Ng H H.Sall4 interacts with Nanog and cooccupies Nanog genomic sites in embryonic stem cells.Journal of Biological Chemistry,2006,281(34):24090-24094
16.Zhang J,Tam W L,Tong G Q,Wu Q,Chan H Y,Soh B S,Lou Y,Yang J,Ma Y,Chai L,Ng H H,Lufkin T,Robson P,Lim B.Sall4modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1.Nature Cell Biology,2006,8(10):1114-1123
17.Buganim Y,Markoulaki S,van Wietmarschen N,Hoke H,Wu T,Ganz K,Akhtar-Zaidi B,He Y,Abraham B J,Porubsky D,Kulenkampff E,Faddah D A,Shi L,Gao Q,Sarkar S,Cohen M,Goldmann J,Nery J R,Schultz M D,Ecker J R,Xiao A,Young R A,Lansdorp P M,Jaenisch R.The developmental potential of i PSCs is greatly influenced by reprogramming factor selection.Cell Stem Cell,2014,15(3):295-309
18.Nichols J,Zevnik B,Anastassiadis K,Niwa H,Klewe-Nebenius D,Chambers I,Sch?ler H,Smith A.Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.Cell,1998,95(3):379-391
19.West F D,Terlouw S L,Kwon D J,Mumaw J L,Dhara S K,Hasneen K,Dobrinsky J R,Stice S L.Porcine induced pluripotent stem cells produce chimeric offspring.Stem Cells and Development,2010,19(8):1211-1220
20.Yang F,Zhang J,Liu Y,Cheng D,Wang H.Structure and functional evaluation of porcine NANOG that is a single-exon gene and has two pseudogenes.International Journal of Biochemistry&Cell Biology,2015,59:142-152
21.Yang F,Ren Y,Li H,Wang H.ESRRB plays a crucial role in the promotion of porcine cell reprograming.Journal of Cellular Physiology,2018,233(2):1601-1611
22.Wang N,Wang Y,Xie Y,Wang H.OTX2 impedes self-renewal of porcine i PS cells through downregulation of NANOG expression.Cell Death and Discovery,2016,2:16090
23.Chen C,Ai H,Ren J,Li W,Li P,Qiao R,Ouyang J,Yang M,Ma J,Huang L.A global view of porcine transcriptome in three tissues from a full-sib pair with extreme phenotypes in growth and fat deposition by paired-end RNA sequencing.BMC Genomics,2011,12(1):448
24.Xiao S,Xie D,Cao X,Yu P,Xing X,Chen C C,Musselman M,Xie M,West F D,Lewin H A,Wang T,Zhong S.Comparative epigenomic annotation of regulatory DNA.Cell,2012,149(6):1381-1392
25.Langmead B,Trapnell C,Pop M,Salzberg S L.Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.Genome Biology,2009,10(3):R25
26.Ma Y,Cui W,Yang J,Qu J,Di C,Amin H M,Lai R,Ritz J,Krause D S,Chai L.SALL4,a novel oncogene,is constitutively expressed in human acute myeloid leukemia(AML)and induces AML in transgenic mice.Blood,2006,108(8):2726-2735
27.Xu K,Chen X,Yang H,Xu Y,He Y,Wang C,Huang H,Liu B,Liu W,Li J,Kou X,Zhao Y,Zhao K,Zhang L,Hou Z,Wang H,Wang H,Li J,Fan H,Wang F,Gao Y,Zhang Y,Chen J,Gao S.Maternal Sall4 Is indispensable for epigenetic maturation of mouse oocytes.Journal of Biological Chemistry,2017,292(5):1798-1807
28.Zhang S,Guo Y,Cui Y,Liu Y,Yu T,Wang H.Generation of intermediate porcine i PS cells under culture condition favorable for mesenchymal-to-epithelial transition.Stem Cell Reviews and Reports,2015,11(1):24-38
29.Larsen K B,Lutterodt M,Rath M F,M?ller M.Expression of the homeobox genes PAX6,OTX2,and OTX1 in the early human fetal retina.International Journal of Developmental Neuroscience,2009,27(5):485-492
30.Simeone A,Acampora D,Mallamaci A,Stornaiuolo A,D’Apice MR,Nigro V,Boncinelli E.A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo.EMBO Journal,1993,12(7):2735-2747
31.Diaczok D,Romero C,Zunich J,Marshall I,Radovick S.A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency.Journal of Clinical Endocrinology and Metabolism,2008,93(11):4351-4359
32.Asadi M H,Khalifeh K,Mowla S J.OCT4 spliced variants are highly expressed in brain cancer tissues and inhibition of OCT4B1causes G2/M arrest in brain cancer cells.Journal of NeuroOncology,2016,130(3):455-463
33.Hwang J Y,Oh J N,Lee D K,Choi K H,Park C H,Lee C K.Identification and differential expression patterns of porcine OCT4variants.Reproduction,2015,149(1):55-66
34.Li D,Yang Z K,Bu J Y,Xu C Y,Sun H,Tang J B,Lin P,Cheng W,Huang N,Cui R J,Yu X G,Zheng X L.OCT4B modulates OCT4Aexpression as ce RNA in tumor cells.Oncology Reports,2015,33(5):2622-2630
35.Tan M H,Au K F,Leong D E,Foygel K,Wong W H,Yao M W.An Oct4-Sall4-Nanog network controls developmental progression in the pre-implantation mouse embryo.Molecular Systems Biology,2013,9(1):632
36.Boyer L A,Lee T I,Cole M F,Johnstone S E,Levine S S,Zucker JP,Guenther M G,Kumar R M,Murray H L,Jenner R G,Gifford DK,Melton D A,Jaenisch R,Young R A.Core transcriptional regulatory circuitry in human embryonic stem cells.Cell,2005,122(6):947-956
37.Chen X,Xu H,Yuan P,Fang F,Huss M,Vega V B,Wong E,Orlov Y L,Zhang W,Jiang J,Loh Y H,Yeo H C,Yeo Z X,Narang V,Govindarajan K R,Leong B,Shahab A,Ruan Y,Bourque G,Sung W K,Clarke N D,Wei C L,Ng H H.Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Cell,2008,133(6):1106-1117
38.Lim C Y,Tam W L,Zhang J,Ang H S,Jia H,Lipovich L,Ng H H,Wei C L,Sung W K,Robson P,Yang H,Lim B.Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages.Cell Stem Cell,2008,3(5):543-554
39.
40.Rao S,Zhen S,Roumiantsev S,Mc Donald L T,Yuan G C,Orkin SH.Differential roles of Sall4 isoforms in embryonic stem cell pluripotency.Molecular and Cellular Biology,2010,30(22):5364-5380
41.Acampora D,Di Giovannantonio L G,Simeone A.Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition.Development,2013,140(1):43-55
42.Buecker C,Srinivasan R,Wu Z,Calo E,Acampora D,Faial T,Simeone A,Tan M,Swigut T,Wysocka J.Reorganization of enhancer patterns in transition from naive to primed pluripotency.Cell Stem Cell,2014,14(6):838-853
43.Yang S H,Kalkan T,Morissroe C,Marks H,Stunnenberg H,Smith A,Sharrocks A D.Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency.Cell Reports,2014,7(6):1968-1981