Liang Jingjia, Shao Wentao, Liu Qian, Lu Qifan, Gu Aihua, Jiang Zhaoyan
Center of Gallbladder Disease, Shanghai East Hospital, Institution of Gallstone Disease, School of Medicine, Tongji University, Shanghai, China.
Key Laboratory of Modern Toxicology of Ministry of Education, State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Front Cell Dev Biol. 2021 Sep 28;9:714271. doi: 10.3389/fcell.2021.714271. eCollection 2021.
Gallstone disease is a worldwide common disease. However, the knowledge concerning the gallbladder in the pathogenesis of cholesterol gallstone formation remains limited. In this study, using single-cell RNA sequencing (scRNA-seq) to obtain the transcriptome of gallbladder cells, we showed cellular heterogeneity and transcriptomic dynamics in murine gallbladder cells during the process of lithogenesis. Our results indicated gallbladder walls were subjected to remodeling during the process of lithogenesis. The major molecular events that happened included proliferation of epithelial cells, infiltration of immune-cells, activation of angiogenesis, and extracellular matrix modulation. Furthermore, we observed partial reversal of gallbladder cell transcriptomes by ursodeoxycholic acid treatment. This work thus provides novel and integral knowledges on the cellular changes during lithogenesis, which is of great significance to the understanding of pathogenesis and treatment of cholesterol gallstone.
胆结石病是一种全球常见疾病。然而，关于胆囊在胆固醇结石形成发病机制中的认识仍然有限。在本研究中，我们使用单细胞RNA测序（scRNA-seq）来获取胆囊细胞的转录组，展示了小鼠胆囊细胞在结石形成过程中的细胞异质性和转录组动态变化。我们的结果表明，在结石形成过程中胆囊壁会发生重塑。发生的主要分子事件包括上皮细胞增殖、免疫细胞浸润、血管生成激活和细胞外基质调节。此外，我们观察到熊去氧胆酸治疗可使胆囊细胞转录组部分逆转。因此，这项工作提供了关于结石形成过程中细胞变化的新颖且完整的知识，这对于理解胆固醇结石的发病机制和治疗具有重要意义。
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