PRC2 specifies ectoderm lineages and maintains pluripotency in primed but not naïve ESCs

Yongli Shan, Zechuan Liang, Qi Xing, Tian Zhang, Bo Wang, Shulan Tian, Wenhao Huang, Yanqi Zhang, Jiao Yao, Yanling Zhu, Ke Huang, Yujian Liu, Xiaoshan Wang, Qianyu Chen, Jian Zhang, Bizhi Shang, Shengbiao Li, Xi Shi, Baojian Liao, Cong ZhangKeyu Lai, Xiaofen Zhong, Xiaodong Shu, Jinyong Wang, Hongjie Yao, Jiekai Chen, Duanqing Pei, Guangjin Pan

Research output: Contribution to journalArticlepeer-review

Abstract

Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages. We further show that polycomb repressive complex 2-deficient mouse embryonic stem cells also release Bmp4 but retain their pluripotency. However, when converted into a primed state, they undergo spontaneous differentiation similar to that of hESCs. In contrast, polycomb repressive complex 2 is dispensable for pluripotency when human embryonic stem cells are converted into the naive state. Our studies reveal both lineage- and pluripotent state-specific roles of polycomb repressive complex 2 in cell fate decisions.

Original languageEnglish (US)
Article number672
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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