IGF2BP1限制了人类原始生殖细胞命运的诱导,以一种m6A-依赖的方式

IGF2BP1限制了人类原始生殖细胞命运的诱导,以一种m6A-依赖的方式

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Jin Zhang¹, Yashi Gu², Lingling Tong¹

¹Center for Regeneration and Cell Therapy of Zhejiang University, University of Edinburgh Institute (ZJU-UoE Institute), Center for Reproductive Medicine of The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.

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概括

通过N6 - - 甲基氨酸 (m6A) 的表观遗传调节会影响生殖细胞的发育. 这项研究揭示了一种m-IGF2BP1-OTX2-MacroH2A.1-TFAP2C通路,它限制了人类原始生殖细胞类细胞的特异性.

科学领域:

发育生物学是发展生物学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
干细胞生物学干细胞生物学

背景情况:

原始生殖细胞 (PGC) 对于将遗传信息跨代传递至关重要.
在PGC规范中N6 - - 甲基氨酸 (m6A) 表观遗传修饰的作用在很大程度上是未知的.

研究的目的:

调查m6A介导表观遗传调节在人类PGC规范中的参与.
确定这个调节途径中的关键分子参与者.

主要方法:

利用3D聚合系统从胚胎干细胞诱导人类PGC类细胞 (hPGCLCs).
进行了基因淘汰和过度表达实验,用于m⁶A编写和除.
确定了m⁶A读者IGF2BP1及其下游目标 (OTX2,TFAP2C) 和相关的组蛋白变体 (MacroH2A.1).
在斑马鱼模型中验证的发现.

主要成果:

破坏m⁶A写字体或过度表达m⁶A erasers增加了hPGCLC的诱导率.
通过稳定OTX2mRNA,IGF2BP1被确定为一个关键的m6阅读器,限制hPGCLC命运.
在生殖细胞特异化过程中,OTX2蛋白通过MacroH2A.1抑制TFAP2C活性.
在斑马鱼PGC诱导中观察到类似的Igf2bp1作用.

结论:

一个m-IGF2BP1-OTX2-MacroH2A.1-TFAP2C信号轴限制了人类生殖细胞命运的规范.
这一途径突显了m6A表谱学在早期生殖细胞发育中的重要性.

关键词:

在IGF2BP1中.麦克罗H2A.1A.1 的情况.OTX2 OTX2 的意思是 PGC 的限制器.根据TFAP2C的规定.m(6) 一个修改修改.原始的生殖细胞.

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