BMP4 Drives Primed to Naïve Transition Through PGC-like State

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 19

PMID 35589713

Authors

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

Affiliations

Soon will be listed here.

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.

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