Single Cell RNA-Sequencing Reveals a Murine Gallbladder Cell Transcriptome Atlas During the Process of Cholesterol Gallstone Formation

Front Cell Dev Biol. 2021 Sep 28;9:714271. doi: 10.3389/fcell.2021.714271. eCollection 2021.

Abstract

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.

Keywords: cholesterol gallstone; gallbladder; lithogenesis; single-cell RNA sequencing; ursodeoxycholic acid.