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H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs

Chen, Jiekai, Liu, He, Liu, Jing, Qi, Jing, Wei, Bei, Yang, Jiaqi, Liang, Hanquan, Chen, You, Chen, Jing, Wu, Yaran, Guo, Lin, Zhu, Jieying, Zhao, Xiangjie, Peng, Tianran, Zhang, Yixin, Chen, Shen, Li, Xuejia, Li, Dongwei, Wang, Tao, Pei, Duanqing·2013·Nature Genetics
DOI 10.1038/ng.2491
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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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Crossref · 10.1038/ng.2491

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  • H3K9me3 inhibits full reprogramming of pre-iPS cells into stem cells, effectively functioning as a barrier to pluripotency.

    “Using this system, Chen and colleagues found that H3K9me3 inhibits full reprogramming of pre-iPS cells into stem cells, effectively functioning as a barrier to pluripotency 88 .”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [88]

  • Pre-iPS cells have embryonic stem cell-like morphology and SSEA-1 expression.

    “These cells, which have embryonic stem cell-like morphology 88 and SSEA-1 expression 85 , may help to identify critical events occurring before cell identity programs are erased.”

    From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [88]

Citations

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Research works printed but not linked: 35

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Metadata

Authors
Chen, J., Liu, H., Liu, J., Qi, J., Wei, B., Yang, J., Liang, H., Chen, Y., Chen, J., Wu, Y., Guo, L., Zhu, J., Zhao, X., Peng, T., Zhang, Y., Chen, S., Li, X., Li, D., Wang, T., & Pei, D.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2012-12-02
Volume
45
Issue
1
Pages
34-42
ISSN
  • 1061-4036
  • 1546-1718
DOI
10.1038/ng.2491
Cited by
462
References
4
Language
en
Licence
www.springer.com/tdm (tdm)

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