BMP4 drives primed to naive transition through PGC-like state

作者：Yu, Shengyong; Zhou, Chunhua; He, Jiangping; Yao, Zhaokai; Huang, Xingnan; Rong, Bowen; Zhu, Hong; Wang, Shijie; Chen, Shuyan; Wang, Xialian; Cai, Baomei; Zhao, Guoqing; Chen, Yuhan; Xiao, Lizhan; Liu, He; Qin, Yue; Guo, Jing; Wu, Haokaifeng; Zhang, Zhen; Zhang, Man; Zhao, Xiaoyang; Lan, Fei; Wang, Yixuan; Chen, Jiekai; Cao, Shangtao^*; Pei, Duanqing^*; Liu, Jing^*

来源：Nature Communications, 2022, 13(1): 2756.

DOI：10.1038/s41467-022-30325-4

• EPIBLAST STEM-CELLS
• GROUND-STATE
• GERM-CELLS
• IN-VITRO
• TRANSCRIPTION
• FATE
• LINEAGE
• SPECIFICATION
• PLURIPOTENCY
• DETERMINANT

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 naive 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(+) naive and c-Kit(-) trophoblast-like cells, among which, the naive 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 naive cells, while Gata2 inhibits PGC-like state by promoting trophoblast-like fate. Our work not only reveals an alternative route for primed to naive transition, but also gains insight into germ cell development. @@@ Multiple pluripotent states have been described in mouse and human stem cells. Here the authors describe trajectories during BMP4 induced primed to naive transition, which bifurcates into naive and trophoblast-like branches with a PGC-like intermediate at the naive branch.

• 单位
  南方医科大学; 中国科学院研究生院; 复旦大学; 广州医学院