BMP4 drives primed to na？ve 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, Jing Liu

Nature Communications

2022, 13, 1, 2756

Jing Liu

17.694

 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 na？ve 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+ na？ve and c-Kit- trophoblast-like cells, among which, the na？ve 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 na？ve cells, while Gata2 inhibits PGC-like state by promoting trophoblast-like fate. Our work not only reveals an alternative route for primed to na？ve transition, but also gains insight into germ cell development.