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单细胞转录组揭示了NASH中C-Kit⁺-肝脏鼻状内皮细胞的新机制

Hui-Yi Li¹, Yu-Xuan Gao¹, Jun-Cheng Wu²

¹Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No. 551, Pudong-South Road, Shanghai, 200120, China.

Cell & bioscience

|March 9, 2024

概括

肝脏的鼻状内皮细胞 (LSEC) 在非酒精性脂肪肝炎 (NASH) 中表现出复杂的反应. 一个特定的LSEC子集,C-Kit+细胞,通过激活髓细胞的作用,有助于NASH恢复.

科学领域:

肝病学肝病学是一种肝病学.
细胞生物学细胞生物学
免疫学免疫学免疫学

背景情况:

非酒精性脂肪肝炎 (NASH) 是一种进展性肝病,其特征是炎症和纤维化.
肝脏的鼻状内皮细胞 (LSECs) 在肝脏稳态和疾病发病过程中起着至关重要的作用.

研究的目的:

在NASH的背景下阐明LSEC的异质性和功能反应.
确定特定的LSEC子集参与NASH进展和潜在的治疗点.

主要方法:

来自对照和NASH小鼠模型 (MCD-fed) 的LSEC单细胞RNA测序.
功能性测定包括共培系统和使用C-Kit+ LSECs的骨髓移植 (BMT).
免疫光染色用于量化人类和小鼠肝脏样本中的LSEC种群.

主要成果:

确定了三个不同的LSEC集群:C-Kit+,Msr1+和Bmp4+/Selp+ VEC,每个都有与NASH相关的独特基因表达特征.
在NASH条件下 (老鼠和人类),C-Kit+ LSECs被降低.
C-Kit+ LSEC移植或共同培养改善了NASH表型,减少了肥胖症,炎症和纤维化,同时促进了抗炎和代谢途径. 这与通过Pink1通路增强的线粒有关.

结论:

在NASH中,LSEC表现出显著的异质性和复杂性,揭示了新的细胞状态.
C-Kit+ LSECs代表了NASH的有希望的治疗标,能够恢复线粒体功能并通过线粒体细胞活化缓解疾病进展.

关键词:

基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因基因肝脏的阴侧内皮细胞 (LSEC)线粒细胞衰变 - - 线粒细胞衰变 (mitophagy) 是一种非酒精性脂肪肝炎 (NASH) 是一种非酒精性脂肪肝炎.单细胞RNA测序 (scRNA-seq) 是一种

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