Dissecting the single-cell transcriptome underlying chronic liver injury

Abstract Chronic liver disease (CLD) is currently a major health problem worldwide, which is accompanied with chronic liver injury and lack clinically effective treatment. However, systematic characterization of chronic liver injury procedure at single-cell resolution is lacking. In the present study, we established chronic liver injury mouse models and conducted single-cell RNA sequencing (scRNA-seq), including choline-deficient, ethionine-supplemented (CDE) and 3,5-diethoxycarbonyl 1,4-dihydrocollidinen (DDC) mouse models. We captured totally 16,389 high-quality cells and identified 12 main cell types in scRNA-seq data. Macrophages and endothelial cells are the largest cell populations in our dataset. Transcriptional trajectory analysis revealed different expression patterns of cells between CDE and DDC models and identified potential liver injury markers, such as Ets1, Gda, Itgam, and Sparc. Differential analysis identified 25 and 152 differentially expressed genes in CDE and DDC macrophages, respectively. In addition, 413 genes were detected to exclusively express in specific pseudo-time states of macrophages. These genes were found to participate in immune-related biological processes. Further cell-cell communication analysis found extensive receding of cell-cell interactions between different cell types in liver injury process, especially in the DDC model. Our study characterized single-cell transcriptional landscape in the process of chronic liver injury, promoting the understanding of the underlying molecular mechanisms and providing candidate clinical strategy for effective intervention of chronic liver diseases.