FoxO转录因子激活了形成性的多能特异基因表达程序
Laura Santini1,2, Saskia Kowald1, Luis Miguel Cerron-Alvan1,2
1Max Perutz Laboratories Vienna, University of Vienna, Vienna BioCenter, 1030, Vienna, Austria.
Nature communications
|September 9, 2024
概括
FoxO转录因子 (TFs) 是细胞命运过渡的关键. 它们从原始多能性退出后进入细胞核,激活形成性多能性增强剂,并建立关键的早期胚胎细胞状态.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 基因规则 基因规则
背景情况:
- 胚胎干细胞 (ESC) 中的原始多能性是由一个特定的基因调节网络 (GRN) 维持的.
- 退出纯粹的多能性涉及到过渡到形成状态,使血统选择,但根本的机制尚未完全理解.
研究的目的:
- 阐明控制从原始多能性过渡到形成多能性的机制.
- 确定启动形成性的GRN所涉及的关键因素.
主要方法:
- 研究了AKT信号和FoxO转录因子 (TF) 在ESC中的作用.
- 在多能性退出期间分析了TF局部化和增强剂结合.
- 评估了FoxO TFs在激活形成性GRN时的必要性和充分性.
主要成果:
- 化AKT作为一个守门员,抑制了FoxO TF在原始ESC中的核定位.
- 退出原始多能性的AKT活动减少允许FoxO TF进入核.
- FoxO TFs结合并激活形成性多能特异增强剂,驱动细胞命运过渡.
结论:
- 福克斯O TFs对于激活形成性多能性GRN至关重要且足够.
- AKT/PTEN/FoxO轴在建立形成性多能性方面发挥着关键作用.
- 这项研究揭示了早期胚胎细胞命运决定的关键机制.
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