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Series GSE17664 Query DataSets for GSE17664
Status Public on Oct 30, 2010
Title Conversion of Epiblast Stem Cells to Embryonic Stem Cells by Small Molecules
Organism Mus musculus
Experiment type Expression profiling by array
Summary Recently, (in vitro) pluripotent EpiSCs were derived from the post-implantation egg cylinder stage epiblasts of mouse and rat. These EpiSCs resemble and correspond very closely to the conventional human embryonic stem cells (hESCs) in the colony morphology and culture/signaling requirements for maintaining pluripotency, but exhibit a range of significant phenotypic and signaling response differences from the conventional mouse ES cells (mESCs). These observations strongly support the notion that EpiSCs and hESCs are intrinsically similar, and raise an attractive hypothesis: as mESCs and EpiSCs/hESCs represent two distinct pluripotency states: the mESC-like state representing the ICM of pre-implantation blastcyst and the EpiSC-like state representing the post-implantation epiblasts, whether the epiblast state (including conventional hESCs) can be converted back to the ICM state. Despite studies providing evidence that epiblast-like cells exist and transition back and forth within colony of conventional mESCs; mESCs and EpiSCs share substantial set of pluripotency transcriptional factors, including Oct4, Sox2 and Nanog; and mESCs are more stable in culture, in the present study we found that EpiSCs differentiated rapidly under mESC culture conditions and no “spontaneously” converted mESC could be readily identified and isolated over serial passages at the population or clonal level. Remarkably, we found that blockage of the TGFβ pathway or inhibition of the H3K4 demethylase LSD1 with small molecule inhibitors induced dramatic morphological changes of EpiSCs towards mESC phenotypes with activation of some ICM-specific gene expression. However, full conversion of EpiSCs to a mESC-like state with competence to chimeric contribution can only be readily generated with a combination of inhibitors of LSD1 and ALK. These observations underscore a powerful and direct induction of reprogramming from the developmentally later-stage EpiSCs to a mESC-like stage by a synergy of signaling and direct epigenetic modulations. It also highlights a significant role for TGFβ pathway inhibition in promoting reprogramming to and sustaining true pluripotency, which further supports our recent studies in generating chimerism-competent rat pluripotent cells. Collectively, our studies provide a proof-of-concept demonstration that pluripotency-restricted EpiSCs can be readily converted to a mESC-like state in the absence of any genetic manipulation by precise pharmacological control of signaling pathways that distinguish the two pluripotency states and an epigenetic target simultaneously, and offer a convenient experimental system to further study the mechanism. Such method and concept may also provide an avenue for generating a new type of mESC-like human pluripotent cell.
 
Overall design Global gene-expression analyses of the parnate/mAMFGi cells
 
Contributor(s) Zhou H, Joo JY, Do JT, Zhu S, Li W, Xiong W, Kim JB, Zhang K, Schöler HR, Ding S
Citation(s) 20705612
Submission date Aug 14, 2009
Last update date Jun 14, 2018
Contact name Hongyan Zhou
Organization name the scripps research institute
Street address 10550 North Torrey Pines Road
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (4)
GSM440910 EpiSCs, biological replicate 1
GSM440911 EpiSCs, biological replicate 2
GSM440912 parnate/mAMFGi, biological replicate 1
Relations
BioProject PRJNA118609

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE17664_RAW.tar 3.1 Mb (http)(custom) TAR
GSE17664_non-normalized.txt.gz 384.1 Kb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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