Transcriptomics,Multiomics

Dataset Information

5

NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 3)


ABSTRACT: The transcription factors Nanog, Oct4 and Sox2 are the master regulators of pluripotency in mouse embryonic stem cells (mESCs), however, their functions in human ESCs (hESCs) have not been rigorously defined. Here we show that the requirements for NANOG, OCT4 and SOX2 in hESCs differ from those in mESCs. Both NANOG and OCT4 are required for self-renewal and repress differentiation. OCT4 controls both extraembryonic and epiblast-derived cell fates in a BMP4-dependent manner. OCT4-depleted hESCs commit to trophectoderm and primitive endoderm in the presence of BMP4, but undergo neuroectoderm differentiation in the absence of BMP4. NANOG represses neuroectoderm and neural crest commitment, but has little or no effect on the other lineages. We find that SOX2 is not required for self-renewal because it is redundant with SOX3, which is induced in SOX2-depleted hESCs. Simultaneous depletion of both SOX2 and SOX3 induces differentiation into the primitive streak. Unexpectedly, we identify significant variability in the usage of pluripotency factors by individual hESC lines, suggesting that the pluripotency network is remodelled to support a continuum of developmental states. Our study revises the general view of how NANOG, OCT4 and SOX2 orchestrate self-renewal in hESCs. Total RNA obtained from SOX2-KD stable hESC clones and H1P control stable hESC clones.

ORGANISM(S): Homo sapiens  

SUBMITTER: Natalia Ivanova  

PROVIDER: E-GEOD-34918 | ArrayExpress | 2012-04-05

SECONDARY ACCESSION(S): GSE34918PRJNA156243

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-34918.README.txt Txt
E-GEOD-34918.additional.1.zip Other
E-GEOD-34918.idf.txt Idf
E-GEOD-34918.processed.1.zip Processed
E-GEOD-34918.sdrf.txt Txt
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Publications

Distinct lineage specification roles for NANOG, OCT4, and SOX2 in human embryonic stem cells.

Wang Zheng Z   Oron Efrat E   Nelson Brynna B   Razis Spiro S   Ivanova Natalia N  

Cell stem cell 20120401 4


Nanog, Oct4, and Sox2 are the core regulators of mouse (m)ESC pluripotency. Although their basic importance in human (h)ESCs has been demonstrated, the mechanistic functions are not well defined. Here, we identify general and cell-line-specific requirements for NANOG, OCT4, and SOX2 in hESCs. We show that OCT4 regulates, and interacts with, the BMP4 pathway to specify four developmental fates. High levels of OCT4 enable self-renewal in the absence of BMP4 but specify mesendoderm in the presence  ...[more]

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