亡抑制将膜肌纤维细胞重编程到管道肌纤维细胞
Maria Jose Gacha-Garay1,2,3, Hui Liu2, Scott E Evans1
1Department of Pulmonary Medicine, the University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
bioRxiv : the preprint server for biology
|June 10, 2025
概括
肺膜肌纤维细胞 (AMF) 在肺部发育后发生亡. 抑制这种编程细胞死亡揭示了AMF可以成熟成为管道肌纤维细胞 (DMF),导致喘类症状.
科学领域:
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 肺部发育涉及气道光滑肌细胞 (ASMCs),管道肌纤维细胞 (DMFs) 和短暂的膜肌纤维细胞 (AMFs).
- 证据表明AMF通过亡后胞形成的清除是有限的.
研究的目的:
- 为了研究肺部发育后膜肌纤维细胞 (AMF) 的命运.
- 为了确定AMF是否经历了亡,并探索它们的潜在可塑性.
主要方法:
- 产生一种可诱导的BCL2过度表达小鼠模型来抑制AMF亡.
- 利用了三个独立的Cre驱动器和单细胞RNA测序 (scRNA-seq).
- 分析了室内灰尘引发的喘模型中的细胞群.
主要成果:
- 经BCL2挽救的AMF在远端气膜管和气膜周围持续存在.
- 持久的AMF突然成熟为DMF类细胞.
- 正常的DMF和被拯救的DMF样细胞都在喘模型中调节了收缩蛋白.
结论:
- AMF的亡清除是肺部发育中的一个关键过程.
- 肺介质细胞表现出命运的可塑性.
- AMF和DMF在肺上皮质轴上表现出病理生理趋同.
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