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在纤维化中追踪肌纤维细胞的起源

Shun He^1,2,3,4, Tianchang Xia^2,3,4, Zhihou Guo^2,3,4

¹Fudan University, Shanghai, China.

Nature communications

|December 21, 2025

概括

居民纤维细胞是纤维化中肌纤维细胞的主要来源,而不是上皮细胞或内皮细胞. 专门的谱系追踪工具揭示了尿和上皮细胞中的部分介质细胞过渡,为慢性病 (CKD) 治疗提供了新的见解.

科学领域:

腎臟病學 (nephrology) 是一種醫學.
细胞生物学细胞生物学
纤维化研究纤维化研究

背景情况:

纤维化是慢性病 (CKD) 的标志,涉及肌纤维细胞的积累.
这些肌纤维细胞的细胞起源,特别是通过像EMT,EndoMT和MMT这样的介质细胞过渡过程,一直受到争议.
了解肌纤维细胞起源对于开发有效的CKD疗法至关重要.

研究的目的:

系统地调查纤维化期间肌纤维细胞的细胞起源.
区分已建立的间酶体过渡通路和其他细胞贡献.
为了确定精确的细胞类型参与肌纤维细胞在纤维化脏的生成.

主要方法:

利用先进的细胞谱系追踪工具来追踪纤维化期间的细胞起源.
开发和应用了新的双重重组合酶介导的血统追踪系统:EMTracer,EndoMTracer和MMTracer.
分析了细胞过渡,包括上皮细胞-介质细胞过渡 (EMT),内皮细胞-介质细胞过渡 (EndoMT) 和巨细胞-介质细胞过渡 (MMT).

主要成果:

没有证据表明EMT,EndoMT或MMT有助于纤维化中的肌纤维细胞群.
确定了居住性纤维细胞作为肌纤维细胞的主要来源.
观察到可逆的部分介质细胞过渡,主要发生在脏尿细胞 (UroCs) 和上皮细胞 (PECs) 中.

结论:

居住性纤维细胞是纤维细胞在纤维化中的主要来源.
在这种情况下,介质细胞过渡并不是通过EMT,EndoMT或MMT对肌纤维细胞形成的重要贡献者.
部分介质细胞过渡发生在尿路和上皮细胞中,为CKD诊断和治疗策略提供了新的视角.

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