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Updated: Jul 2, 2025

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单细胞转录组分析确定了肝硬化期间介质细胞分化中的核心基因和转录因子

Xue Dai¹, Hui-Lin Zheng¹, Ya-Xin Ma¹

¹College of Biological and Chemical Engineering, Zhejiang University of Science and Technology, 310023 Hangzhou, Zhejiang, China.

Frontiers in bioscience (Landmark edition)

|February 29, 2024

概括

这项研究揭示了关键的基因和转录因子驱动肝细胞纤维化中的肝细胞变化. 它通过了解细胞分化和逆转机制,突出显示了肝纤维化的潜在治疗点.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
肝病学肝病学是一种肝病学.

背景情况:

介质细胞,包括肝星细胞 (HSC),纤维细胞 (FB),肌纤维细胞 (MFB) 和血管光滑肌细胞 (VSMC),对于肝脏稳态和纤维化至关重要.
了解这些细胞的动态进化对于探索肝纤维化及其向肝硬化进展的可逆机制至关重要.

研究的目的:

为了重建肝细胞介质细胞的进化轨迹,从健康状态到肝硬化状态.
为了确定核心基因和转录因子 (TFs) 参与介质细胞分化和逆转在肝纤维化.

主要方法:

来自超过5万个人类单细胞 (健康肝脏和肝硬化肝脏) 和小鼠肝脏介质细胞的转录组分析.
对经过激活和非激活 (TGF-β1受刺激) 的高细胞的大量RNA测序数据进行整合性分析.

主要成果:

鉴定了关键基因 (例如NR1H4,ZEB家族) 和TFs在介质细胞分化中.
在肝硬化患者中观察到VSMC转化为HSC和HSC转化为MFB分化,其中一些MFB恢复为无活化的HSC (iHSC).
鼠标模型显示了类似的轨迹,但在细胞亚种群逆转方面有所不同,这表明反映人类疾病进展的局限性.

结论:

使用scRNA-seq和大量RNA-seq数据在肝纤维化期间介质细胞分化和逆转过程中解析的初级基因和TFs.
在HSC激活到MFB和MFB逆转到iHSC中证明了核心基因和TFs.
确定了肝纤维化的有希望的治疗点,并提供了对其分子机制的见解.

关键词:

RNA的速度RNA的速度肝脏的恒星细胞.肝脏纤维化肝脏纤维化一个单面的单.肌纤维母细胞细胞.单细胞RNA测序 (scRNA-seq) 是一种

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