title: Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs.
abstract: SOX2 is a key regulator of multiple types of stem cells, especially embryonic stem cells (ESCs) and neural progenitor cells (NPCs). Understanding the mechanism underlying the function of SOX2 is of great importance for realizing the full potential of ESCs and NPCs. Here, through genome-wide comparative studies, we show that SOX2 executes its distinct functions in human ESCs (hESCs) and hESC-derived NPCs (hNPCs) through cell type- and stage-dependent transcription programs. Importantly, SOX2 suppresses non-neural lineages in hESCs and regulates neurogenesis from hNPCs by inhibiting canonical Wnt signaling. In hESCs, SOX2 achieves such inhibition by direct transcriptional regulation of important Wnt signaling modulators, WLS and SFRP2. Moreover, SOX2 ensures pluripotent epigenetic landscapes via interacting with histone variant H2A.Z and recruiting polycomb repressor complex 2 to poise developmental genes in hESCs. Together, our results advance our understanding of the mechanism by which cell type-specific transcription factors control lineage-specific gene expression programs and specify cell fate.
authors.affiliation: Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai 200031, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Zhou
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai 200031, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Molecular Developmental Biology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
authors.forename: Hongyao
authors.initials: H
authors.lastname: Yu
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai 200031, China.|Laboratory of Molecular Developmental Biology, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D006657:Histones; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors
references.citation: Cell. 2008 Nov 14;135(4):649-61
references.pmid: 18992931
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18598-603
references.pmid: 19841259
references.citation: Cell Stem Cell. 2012 Mar 2;10(3):312-26
references.pmid: 22385658
references.citation: Nat Rev Genet. 2011 Apr;12(4):283-93
references.pmid: 21358745
references.citation: Stem Cells. 2015 Jul;33(7):2126-34
references.pmid: 25809870
references.citation: Nat Rev Mol Cell Biol. 2006 Jul;7(7):540-6
references.pmid: 16723974
references.citation: Cell Stem Cell. 2012 Apr 6;10(4):440-54
references.pmid: 22482508
references.citation: Nat Med. 2004 Jan;10(1):55-63
references.pmid: 14702635
references.citation: Nat Commun. 2013;4:2610
references.pmid: 24162018
references.citation: Science. 1998 Nov 6;282(5391):1145-7
references.pmid: 9804556
references.citation: Nat Cell Biol. 2007 Jun;9(6):625-35
references.pmid: 17515932
references.citation: EMBO Mol Med. 2012 Jan;4(1):38-51
references.pmid: 22147553
references.citation: Stem Cells. 2010 Oct;28(10):1741-50
references.pmid: 20734356
references.citation: Cell Stem Cell. 2012 Nov 2;11(5):589-95
references.pmid: 23122286
references.citation: F1000Prime Rep. 2015 Jan 05;7:01
references.pmid: 25705384
references.citation: BMC Genomics. 2009;10:10
references.pmid: 19128516
references.citation: Curr Opin Genet Dev. 2008 Apr;18(2):109-15
references.pmid: 18339538
references.citation: Genome Biol. 2012;13(10):R85
references.pmid: 23034477
references.citation: J Gastroenterol Hepatol. 2013 Mar;28(3):551-9
references.pmid: 23215838
references.citation: Nat Biotechnol. 2009 Mar;27(3):275-80
references.pmid: 19252484
references.citation: Cell Stem Cell. 2013 Jan 3;12(1):15-30
references.pmid: 23290134
references.citation: Nucleus. 2014 Jan-Feb;5(1):21-7
references.pmid: 24637397
references.citation: Nat Neurosci. 2009 Sep;12(9):1079-81
references.pmid: 19710645
references.citation: Cell. 2012 Dec 21;151(7):1608-16
references.pmid: 23260146
references.citation: Stem Cells. 2008 Aug;26(8):1931-8
references.pmid: 18388306
references.citation: Cell. 2006 Apr 21;125(2):301-13
references.pmid: 16630818
references.citation: Stem Cells. 2014 Dec;32(12):3196-208
references.pmid: 25100239
references.citation: Genes Dev. 2006 May 1;20(9):1187-202
references.pmid: 16651659
references.citation: Cell Death Dis. 2013;4:e695
references.pmid: 23807224
references.citation: Nat Cell Biol. 2008 Feb;10(2):178-85
references.pmid: 18193032
references.citation: Nat Genet. 2009 Aug;41(8):941-5
references.pmid: 19633671
references.citation: Stem Cell Reports. 2014 Dec 9;3(6):1015-28
references.pmid: 25458891
references.citation: PLoS Genet. 2013;9(2):e1003288
references.pmid: 23437007
references.citation: Genes Cells. 2010 May;15(5):455-70
references.pmid: 20384793
references.citation: Mol Cancer Ther. 2013 May;12(5):685-95
references.pmid: 23604067
references.citation: Nature. 2015 Feb 19;518(7539):355-9
references.pmid: 25533951
references.citation: Nature. 2015 Feb 19;518(7539):413-6
references.pmid: 25487152
references.citation: Stem Cell Reports. 2015 Jan 13;4(1):114-28
references.pmid: 25544567
references.citation: Mol Cell Neurosci. 2007 Nov;36(3):408-15
references.pmid: 17822920
references.citation: Development. 2006 Mar;133(6):989-99
references.pmid: 16467359
references.citation: Neuron. 2003 Aug 28;39(5):749-65
references.pmid: 12948443
references.citation: Development. 2011 Oct;138(19):4179-84
references.pmid: 21896628
references.citation: Cold Spring Harb Perspect Biol. 2013 Mar;5(3):a015081
references.pmid: 23085770
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E3017-26
references.pmid: 23884650
references.citation: Proteomics. 2011 Mar;11(5):921-34
references.pmid: 21280222
references.citation: Cell Stem Cell. 2014 Sep 4;15(3):281-94
references.pmid: 25192463
references.citation: Mol Cell. 2013 Aug 8;51(3):349-59
references.pmid: 23932716
references.citation: Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4485-90
references.pmid: 22392999
references.citation: Cell Stem Cell. 2013 Feb 7;12(2):180-92
references.pmid: 23260488
references.citation: Genes Dev. 2012 Mar 1;26(5):461-73
references.pmid: 22391449
references.citation: Mol Hum Reprod. 2008 Mar;14(3):169-79
references.pmid: 18263607
references.citation: In Vitro Cell Dev Biol Anim. 2010 Apr;46(3-4):186-91
references.pmid: 20186511
references.citation: EMBO Mol Med. 2012 Dec;4(12):1294-307
references.pmid: 23129487
references.citation: EMBO Rep. 2015 Sep;16(9):1177-91
references.pmid: 26265007
references.citation: Development. 2009 Oct;136(19):3289-99
references.pmid: 19736324