BMP4 drives primed to naïve transition through PGC-like state

Shengyong Yu, Chunhua Zhou, Jiangping He, Zhaokai Yao, Xingnan Huang, Bowen Rong, Hong Zhu, Shijie Wang, Shuyan Chen, Xialian Wang, Baomei Cai, Guoqing Zhao, Yuhan Chen, Lizhan Xiao, He Liu, Yue Qin, Jing Guo, Haokaifeng Wu, Zhen Zhang, Man Zhang, Xiaoyang Zhao, Fei Lan, Yixuan Wang, Jiekai Chen, Shangtao Cao (), Duanqing Pei () and Jing Liu ()
Additional contact information
Shengyong Yu: Chinese Academy of Sciences
Chunhua Zhou: Chinese Academy of Sciences
Jiangping He: Bioland Laboratory
Zhaokai Yao: Southern Medical University
Xingnan Huang: Westlake University
Bowen Rong: Fudan University
Hong Zhu: Chinese Academy of Sciences
Shijie Wang: Guangzhou Medical University
Shuyan Chen: Chinese Academy of Sciences
Xialian Wang: Guangzhou Medical University
Baomei Cai: Bioland Laboratory
Guoqing Zhao: Bioland Laboratory
Yuhan Chen: Southern Medical University
Lizhan Xiao: Bioland Laboratory
He Liu: Bioland Laboratory
Yue Qin: Chinese Academy of Sciences
Jing Guo: Chinese Academy of Sciences
Haokaifeng Wu: Chinese Academy of Sciences
Zhen Zhang: Chinese Academy of Sciences
Man Zhang: Bioland Laboratory
Xiaoyang Zhao: Southern Medical University
Fei Lan: Fudan University
Yixuan Wang: Chinese Academy of Sciences
Jiekai Chen: Chinese Academy of Sciences
Shangtao Cao: Bioland Laboratory
Duanqing Pei: Westlake University
Jing Liu: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Multiple pluripotent states have been described in mouse and human stem cells. Here, we apply single-cell RNA-seq to a newly established BMP4 induced mouse primed to naïve transition (BiPNT) system and show that the reset is not a direct reversal of cell fate but goes through a primordial germ cell-like cells (PGCLCs) state. We first show that epiblast stem cells bifurcate into c-Kit+ naïve and c-Kit− trophoblast-like cells, among which, the naïve branch undergoes further transition through a PGCLCs intermediate capable of spermatogenesis in vivo. Mechanistically, we show that DOT1L inhibition permits the transition from primed pluripotency to PGCLCs in part by facilitating the loss of H3K79me2 from Gata3/6. In addition, Prdm1/Blimp1 is required for PGCLCs and naïve cells, while Gata2 inhibits PGC-like state by promoting trophoblast-like fate. Our work not only reveals an alternative route for primed to naïve transition, but also gains insight into germ cell development.

Date: 2022
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DOI: 10.1038/s41467-022-30325-4

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