H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs

被引：392

作者：

Chen, Jiekai ^{[1
,2
]}

Liu, He ^{[1
,2
]}

Liu, Jing ^{[1
,2
]}

Qi, Jing ^{[1
,2
]}

Wei, Bei ^{[1
,2
]}

Yang, Jiaqi ^{[1
,2
]}

Liang, Hanquan ^{[1
,2
]}

Chen, You ^{[1
,2
]}

Chen, Jing ^{[1
,2
]}

Wu, Yaran ^{[1
,2
]}

Guo, Lin ^{[1
,2
]}

Zhu, Jieying ^{[1
,2
]}

Zhao, Xiangjie ^{[1
,2
]}

Peng, Tianran ^{[1
,2
]}

Zhang, Yixin ^{[1
,2
]}

Chen, Shen ^{[1
,2
]}

Li, Xuejia ^{[1
,2
]}

Li, Dongwei ^{[1
,2
]}

Wang, Tao ^{[1
,2
]}

Pei, Duanqing ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Key Lab Regenerat Biol, S China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China

[2] Chinese Acad Sci, Guangdong Prov Key Lab Stem Cell & Regenerat Med, S China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed & Hlth, Guangzhou, Guangdong, Peoples R China

来源：

NATURE GENETICS | 2013年 / 45卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PLURIPOTENT STEM-CELLS; SELF-RENEWAL; FIBROBLASTS; INDUCTION; GENERATION; KLF4;

D O I：

10.1038/ng.2491

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：34 / U62

页数：10

共 39 条

[21] Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells [J].