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Updated: Jul 26, 2025

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De Novo Generation of Somatic Stem Cells by YAP/TAZ
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释放由YAP功能障碍引起的复制性毒性使中酶体干细胞复原
Fanyuan Yu1,2, Lin Yao1,2, Feifei Li1
1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Aging cell
|June 21, 2023
概括
YAP功能障碍导致细胞衰老. 依赖海马的YAP活动通过调节细胞循环和DNA修复来控制介质细胞 (MSCs) 中的复制性衰老,突变使MSCs再生.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- hippo-independent YAP 功能障碍损害了核外的完整性,导致 stromal 细胞的时间老化.
- 细胞衰老,特别是介质细胞 (MSCs) 中的复制性衰老,是衰老的关键因素.
研究的目的:
- 调查YAP在MSCs复制性衰老中的依赖Hippo酸化的作用.
- 阐明YAP在控制细胞衰老和基因组稳定的下游机制.
主要方法:
- 利用MSCs的体外扩张来研究复制性衰老.
- 使用Hippo-off YAP突变 (YAPS127A/S381A) 来评估YAP的功能.
- 分析了YAP/TEAD对RRM2表达的调节及其对细胞周期进展的影响.
- 研究了YAP对复制性毒性 (RT) 转录组学和DNA损伤反应/修复途径的控制.
主要成果:
- 河马酸化减少了核YAP,降低了YAP蛋白水平,并启动了复制性衰老.
- YAP/TEAD控制RRM2表达,促进G1/S过渡并释放复制性毒性.
- YAP调节RT转录组学,延迟基因组不稳定性并增强DNA修复.
- 基因组YAP突变通过维持细胞周期,减少基因组不稳定性,恢复再生能力而没有瘤发生风险,使MSC复苏.
结论:
- 由Hippo酸化调节的YAP活动,通过NE完整性独立路径在MSCs的复制性衰老中起着至关重要的作用.
- 针对YAP信号提供了一种潜在的策略,可以使老化的细胞复苏并恢复组织功能.
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