H3K9 methylation is a barrier during somatic cell reprogramming into iPSCs

作者：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^*

来源：Nature Genetics, 2013, 45(1): 34-U62.

DOI：10.1038/ng.2491

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

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.

• 单位
  中国科学院广州生物医药与健康研究院