异步的小鼠胚胎极化导致细胞命运规范的异质性
Adiyant Lamba1, Meng Zhu1,2, Maciej Meglicki1
1Mammalian Embryo and Stem Cell Group, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
eLife
|December 8, 2025
概括
早期和晚期的8细胞阶段小鼠胚胎显示出明显的两极分化,影响了谱系规范. 在4细胞阶段减少CARM1活动促进了早期的极化和 trofhectoderm命运.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 遗传学 遗传学 是一个
背景情况:
- 哺乳动物胚胎中的第一个血统分离将内部细胞质 (ICM) 与托菲克托皮 (TE) 分离.
- 这一过程涉及8细胞阶段的细胞极化和不对称的细胞分裂.
- 先前的细胞异质性,如在4细胞阶段改变的CARM1活性,也可能影响谱系分配.
研究的目的:
- 为了研究小鼠胚胎中细胞极化异步的性质.
- 确定将早期细胞不对称性与后来的血统规范联系起来的分子机制.
- 阐明CARM1及其基质BAF155在托菲克托皮 (TE) 命运决定中的作用.
主要方法:
- 分析小鼠胚胎极化时间和细胞形态.
- 在8细胞阶段的不同阶段对细胞进行分子分析.
- 研究CARM1活动调制对谱系规范的影响.
主要成果:
- 在8细胞阶段的小鼠胚胎极化是异步的,早期和晚期极化细胞具有不同的特性.
- 早期的极化细胞倾向于托菲克托皮 (TE) 谱系的特异性.
- 降低CARM1活性和增加BAF155水平促进早期极化和TE特异化.
结论:
- 在8细胞阶段的异步极化是哺乳动物早期发育的关键机制.
- 在4细胞阶段不对称性 (CARM1活性) 和8细胞阶段极化之间存在联系.
- 这些发现整合了以前独立的机制,控制了第一个胚胎血统分配.
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