浙江大学陈迪小组的一项最新研究的研究显示，IGF2BP1以依赖m⁶A的方式限制人类原始生殖细胞命运的诱导。2025年5月27日出版的《细胞—干细胞》杂志发表了这项成果。

在这项研究中，研究小组报道了m⁶A写入者的敲除或m⁶A擦除者的过表达导致胚胎干细胞诱导的人类PGC样细胞（hPGCLCs）的百分比增加，这些细胞形成了一个3D聚集体系统。该研究组发现m⁶A阅读器IGF2BP1是通过以m⁶A依赖的方式稳定OTX2 mRNA来限制hPGCLC命运诱导的关键因素。反过来，OTX2蛋白通过组蛋白变体MacroH2A.1抑制TFAP2C的功能。该团队还观察到Igf2bp1在斑马鱼诱导PGC命运中的类似作用。总之，该课题组鉴定了一个m⁶A-IGF2BP1-OTX2-MacroH2A。限制人类生殖细胞命运规范的1-TFAP2C信号轴。

研究人员表示，原始生殖细胞（PGCs）在胚胎发生的早期就被指定，并建立生殖细胞谱系，将遗传和表观遗传信息从父母传递给后代。然而，^N6-甲基腺苷（m6A）介导的表观遗传调控是否参与了PGCs的规范尚不清楚。

附：英文原文

Title: IGF2BP1 restricts the induction of human primordial germ cell fate in an m6A-dependent manner

Author: Jin Zhang, Yashi Gu, Lingling Tong, Boshi Feng, Shenghua Dong, Qizhe Shao, Yanxi Chen, Huanchang Tu, Ziqi Wang, Yueqi Wang, Xiang Li, Honglin Yu, Ziying Lin, Xueting Wang, Zhenfu Li, Zhipeng Ai, Yangquan Xiang, Zhiwei Jiang, Zixin Jin, Zhengyi Li, Yuxin Chen, Zuolin Shen, Chenyang Huang, Jianzhao Liu, Jian Liu, Pengfei Xu, You Yu, Peng Xia, Hongqing Liang, Huilin Huang, Di Chen

Issue&Volume: 2025-05-27

Abstract: Primordial germ cells (PGCs) are specified early during embryogenesis and establish the germ cell lineage for transmitting genetic and epigenetic information from parents to offspring. However, whether N6-methyladenosine (m6A)-mediated epigenetic regulation is involved in the specification of PGCs remains elusive. In this study, we report that a knockout of m6A writers or overexpression of m6A erasers leads to an increased percentage of human PGC-like cells (hPGCLCs) induced from embryonic stem cells using a 3D aggregate system. We identify the m6A reader IGF2BP1 as the key factor for restricting hPGCLC fate induction by stabilizing OTX2 mRNAs in an m6A-dependent manner. In turn, OTX2 protein suppresses the function of TFAP2C via histone variant MacroH2A.1 during germ cell lineage specification. We also observe a similar role of Igf2bp1 in zebrafish in the induction of PGC fate. In summary, we identify an m6A-IGF2BP1-OTX2-MacroH2A.1-TFAP2C signaling axis that restricts the specification of human germ cell fate.

DOI: 10.1016/j.stem.2025.05.001

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00181-X