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Title: NANOG-OCT4-SOX2 Regulatory Module in Human Embryonic Stem Cells (dataset 1)      
dateReleased:
04-05-2012
description:
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 H1P (control)-, shNANOG (Nanog shRNA knockdown)-, shOCT4 (Oct4 shRNA knockdown)- or shSOX2 (Sox2 shRNA knockdown)-transduced hESCs for 8 days time course.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-34904
refinement:
raw
alternateIdentifiers:
34904
keywords:
functional genomics
dateModified:
06-25-2012
creators:
Natalia Ivanova
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-10558
name:
Illumina HumanHT-12 V4.0 expression beadchip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-34904/E-GEOD-34904.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-34904/E-GEOD-34904.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE34904
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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