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NR5A2将阴茎基因组激活与全能胚胎中的第一系分离联系起来

Fangnong Lai^1,2, Lijia Li^1,2, Xiaoyu Hu^1,2

¹Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, New Cornerstone Science Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.

|November 7, 2023

概括

核受体NR5A2对于将胚胎基因组激活与小鼠胚胎中的早期血统分离联系起来至关重要. 它的缺失会损害基因激活,导致在毛囊阶段的发育停止.

科学领域:

发展生物学发展生物学
遗传学遗传学是一种遗传学.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

紫毒基因组激活 (ZGA) 启动胚胎基因表达.
在哺乳动物中,ZGA与第一个细胞系分离 (ICM与托菲克托德) 之间的联系尚不清楚.
核受体 (NR) 是转录因子 (TF),涉及早期发育.

研究的目的:

调查NR TFs在将ZGA连接到血统分离中的作用.
确定NR5A2在小鼠胚胎早期发育中的功能.
阐明NR5A2如何在2细胞 (2C) 到8细胞 (8C) 阶段调节基因表达.

主要方法:

Nr5a2 在小鼠胚胎中的敲除和敲除.
全基因组染色体结合分析 (ChIP-seq).
分析不同胚胎阶段的基因表达模式.

主要成果:

NR5A2在ZGA上被诱导,对4-8C特异性基因激活至关重要.
Nr5a2 缺乏导致尽管ZGA正常,但在毛囊阶段停止.
NR5A2与包括B1元素在内的cis调节元件结合,对于打开8C特定结合位点至关重要.
NR5A2调节了关键的多能性 (Nanog, Pou5f1/Oct4) 和谱系特异性 (Gata6, Tead4, Gata3) 基因.

结论:

在小鼠胚胎中,NR5A2充当ZGA和第一个血统分离之间的关键桥梁.
NR5A2控制了早期细胞命运决定所需的特定监管元素的可访问性.
这项研究确定NR5A2是全能性和早期谱系规范的关键调节者.

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