Pluto Bioinformatics

GSE92625: PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not nave ESCs

Bulk RNA sequencing

We generated deletion of core components of PRC2 in human embryonic stem cells, (H1, H1-EZH1-/-, H1-EZH2-/-, H1-EED-/-, H1-SUZ12-/- H1-EZH2-/-/EZH1-/-) respectively. Every cell line has been sequenced for two times. And we analyzed whole transcriptome expression profile in different cell lines. Our results revealed that the H1-EZH1-/- and H1-EZH2-/- stay very close to WT(H1) hESCs based on correlations of whole genome transcription, and showed that a highly close related differentiation phenotype between EED-/-H1, SUZ12-/-H1 and EZH2-/-/ EZH1-/-H1 hESCs compared with WT(H1) hESCs. To study why deletion of core components of PRC2 induced spontaneous differentiation in human ESCs. We introduced an inducible system to over-express(OE) EED in hESCs and subsequently performed gene targeting to knock-out the endogenous EED in these cells. In the presence of DOX, H1-EED-/-/EED-OE maintained the undifferentiated state. However, H1-EED-/-/EED-OE initiated the gradual and spontaneous differentiation after withdrawal of DOX at different days. Our results revealed that TGFb/BMPs signaling factors were clearly up-regulated at very early stage of DOX withdrawal, at which time no obvious differentiation has been detected based on morphology and the transcriptome data. Our study revealed PRC2 is indispensable for maintaining pluripotency in human embryonic stem cells(ESCs) through inhibiting BMPs singaling. SOURCE: qianyu chen ( - Guangjin Pan Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences

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