The Role of SOX2 in Maintaining Pluripotency and Differentiation of Human Embryonic Stem Cells

Adachi, Keiko; Suemori, Hirofumi; Nakatsuji, Norio; Kawase, Eihachiro

doi:10.5772/23094

Cited by 52 publications

(65 citation statements)

References 48 publications

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“…S5B). This phenotype is consistent with the underlying hypothesis of SCC working as an O/S transcriptional coactivator, because knockdown of either TF results in loss of pluripotency and induction of trophectoderm differentiation (26,(28)(29)(30). Down-regulation of pluripotency genes also translated to a reduction in protein levels ( Fig.…”

Section: Rad23b Targets Gene Promoters and Distal Regulatory Regions Insupporting

confidence: 75%

Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells

Cattoglio

Zhang

Grubisic

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The embryonic stem cell (ESC) state is transcriptionally controlled by OCT4, SOX2, and NANOG with cofactors, chromatin regulators, noncoding RNAs, and other effectors of signaling pathways. Uncovering components of these regulatory circuits and their interplay provides the knowledge base to deploy ESCs and induced pluripotent stem cells. We recently identified the DNA-repair complex xeroderma pigmentosum C (XPC)-RAD23B-CETN2 as a stem cell coactivator (SCC) required for OCT4/SOX2 transcriptional activation. Here we investigate the role of SCC genome-wide in murine ESCs by mapping regions bound by RAD23B and analyzing transcriptional profiles of SCC-depleted ESCs. We establish OCT4 and SOX2 as the primary transcription factors recruiting SCC to regulatory regions of pluripotency genes and identify the XPC subunit as essential for interaction with the two proteins. The present study reveals new mechanistic and functional aspects of SCC transcriptional activity, and thus underscores the diversified functions of this regulatory complex.transcription | pluripotency | protein-protein interactions | ChIP-seq | RNA-seq

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Section: Rad23b Targets Gene Promoters and Distal Regulatory Regions Insupporting

confidence: 75%

Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells

Cattoglio

Zhang

Grubisic

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Effect of C3B3 on b-catenin and pluripotency-associated transcription factors Because Wnt/b-catenin signaling molecules are implicated in the maintenance of pluripotency-associated transcription factors, 24,25 we further evaluated mRNA expression of Sox2, [33][34][35] Oct3/4, 36,37 Nanog, 38,39 Klf-4 and Bmi-1. 40 Notably, Nanog and b-catenin were more highly expressed in SP fraction than in MP fraction of RPMI 8226 cells (Figure 6a).…”

Section: Rpmi8226mentioning

confidence: 99%

Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors

et al. 2012

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“…To date, most studies on SOX2 were conducted in mouse cells or animal models. The role of SOX2 in human ESCs (hESCs) and human NPCs (hNPCs) is poorly defined; controversies remain regarding differentiated lineages after silencing SOX2 in hESCs [3,4]. Recently, Wang et al [5] reported that SOX2 knockdown (KD) caused a compensational increase in SOX3 expression and that simultaneous depletion of SOX2 and SOX3 led to primitive streak induction in hESCs.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs

et al. 2016

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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.

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The Role of SOX2 in Maintaining Pluripotency and Differentiation of Human Embryonic Stem Cells

Cited by 52 publications

References 48 publications

Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells

Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells

Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors

Comprehensive profiling reveals mechanisms of SOX2-mediated cell fate specification in human ESCs and NPCs

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