血统调节器TFAP2C和NR5A2在全能胚胎中充当双能激活剂
Lijia Li1,2, Fangnong Lai1,2, Ling Liu1,2
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.
Nature structural & molecular biology
|January 19, 2024
概括
在小鼠胚胎发育初期,TFAP2C和NR5A2激活了细胞内质量 (ICM) 和肌体内质量 (TE) 基因,揭示了独特的全能性调节电路.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 哺乳动物的胚胎发育涉及早期的血统分离到内部细胞质 (ICM) 和体 (TE).
- 通过转录因子 (TFs) 了解这些第一个细胞命运决定的体内调节至关重要,但具有挑战性.
- 现有的TF regulomes通常是从细胞培养中推断出来的,而不是早期胚胎.
研究的目的:
- 在早期小鼠胚胎的初始谱系规范过程中调查转录因子规律体.
- 阐明TFAP2C和NR5A2在全能性和早期血统承诺中的作用.
- 将TF绑定和激活映射到不同的发展阶段:预启动,启动,承诺和维护.
主要方法:
- 在早期小鼠胚胎中对TF结合和基因激活的体内研究.
- 分析TFAP2C和NR5A2规律体在全能 (二至八细胞) 和胚胎细胞阶段的分析.
- 在TFAP2C缺陷后评估基因表达,细胞亡和细胞数量.
主要成果:
- 在全能阶段,TFAP2C结合并激活早期ICM和TE基因 ("双能激活").
- 缺少Tfap2c会导致关键ICM和TE基因的下调,导致胚芽细胞的发育缺陷.
- 在结合过程中,TFAP2C动态地将结合从早期的ICM基因转移到晚期的TE和胚胎外外皮 (ExE) 基因.
- NR5A2还表现出"双能激活",在八细胞阶段结合和激活ICM和TE两种基因.
结论:
- 在哺乳动物胚胎中,TFAP2C和NR5A2在调节最早的细胞命运决定方面发挥着至关重要的作用.
- 一个独特的转录电路是全能性的基础,涉及可适应的谱系调节器.
- 这些发现为管理哺乳动物胚胎系谱规范的体内机制提供了新的见解.
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