在PDGFRα表达膜纤维细胞中的YAP/TAZ活性通过Wnt4调节AT2扩散
Jane Y Song1, Fabien Wehbe2, Aaron K Wong3
1Department of Immunology Discovery, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Cell reports
|May 7, 2025
概括
河马通路中的YAP/TAZ蛋白调节肺纤维细胞功能. 抑制纤维细胞中的这些蛋白质通过Wnt4信号增强了它们对膜干细胞的支持,促进了肺部的修复.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 肺部医学 肺部医学
背景情况:
- 涉及Yes关联蛋白1 (YAP) 和WW域含有转录调节器1 (TAZ) 的Hippo通路对于肺部平衡和修复至关重要.
- 虽然YAP/TAZ在肺上皮细胞中的作用已知,但它们在肺纤维细胞中的功能不太清楚.
研究的目的:
- 研究YAP/TAZ在肺纤维细胞中在支持膜干细胞和肺修复中的作用.
- 阐明纤维细胞YAP/TAZ影响肺细胞增殖的分子机制.
主要方法:
- 产生了一种小鼠模型,用于特别在纤维细胞中诱导YAP/TAZ的淘汰.
- 利用单细胞分析和表观遗传学分析来研究纤维细胞和上皮细胞的变化.
- 进行了计算和体内分析,以评估Wnt信号和细胞增殖.
主要成果:
- 纤维细胞特异性YAP/TAZ敲除增强了PDGFRα+膜纤维细胞对膜干细胞衍生器官的支持.
- 在YAP/TAZ抑制后,单细胞分析确定了Wnt4+丰富的纤维细胞亚群.
- 纤维细胞中YAP/TAZ抑制导致Wnt信号和Wnt4分泌的增加,促进了膜2型 (AT2) 细胞的增殖.
结论:
- 在PDGFRα+膜纤维细胞中,YAP/TAZ在维持和促进AT2细胞增殖方面发挥着至关重要的作用.
- 纤维细胞衍生的Wnt4是YAP/TAZ在支持肺干细胞和修复的功能中的关键调解者.
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