H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs - PubMed (original) (raw)

doi: 10.1038/ng.2491. Epub 2012 Dec 2.

He Liu, Jing Liu, Jing Qi, Bei Wei, Jiaqi Yang, Hanquan Liang, You Chen, Jing Chen, Yaran Wu, Lin Guo, Jieying Zhu, Xiangjie Zhao, Tianran Peng, Yixin Zhang, Shen Chen, Xuejia Li, Dongwei Li, Tao Wang, Duanqing Pei

Affiliations

• PMID: 23202127
• DOI: 10.1038/ng.2491

H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs

Jiekai Chen et al. Nat Genet. 2013 Jan.

Abstract

The induction of pluripotent stem cells (iPSCs) by defined factors is poorly understood stepwise. Here, we show that histone H3 lysine 9 (H3K9) methylation is the primary epigenetic determinant for the intermediate pre-iPSC state, and its removal leads to fully reprogrammed iPSCs. We generated a panel of stable pre-iPSCs that exhibit pluripotent properties but do not activate the core pluripotency network, although they remain sensitive to vitamin C for conversion into iPSCs. Bone morphogenetic proteins (BMPs) were subsequently identified in serum as critical signaling molecules in arresting reprogramming at the pre-iPSC state. Mechanistically, we identified H3K9 methyltransferases as downstream targets of BMPs and showed that they function with their corresponding demethylases as the on/off switch for the pre-iPSC fate by regulating H3K9 methylation status at the core pluripotency loci. Our results not only establish pre-iPSCs as an epigenetically stable signpost along the reprogramming road map, but they also provide mechanistic insights into the epigenetic reprogramming of cell fate.

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