A comprehensive molecular atlas of the mesenchymal cell types in the mouse liver.

Abstract

The liver plays crucial roles in many essential physiological processes, and its impaired function due to liver fibrosis from various causes is an increasingly significant health issue. The liver's functionality relies on the precise arrangement of its cellular structures, yet the molecular architecture of these units remains only partially understood. We created a comprehensive molecular atlas detailing the major cell types present in the adult mouse liver through deep single-cell RNA sequencing. Our analysis offers new insights into hepatic endothelial and mesenchymal cells, specifically highlighting the diversity of cells in the periportal microvasculature, the sinusoids, and the portal vein, the latter exhibiting a mixed arterio-venous phenotype. We identified distinct subpopulations of hepatic stellate cells, fibroblasts, and vascular mural cells located in different anatomical liver regions. Comparisons with transcriptomic data from disease models indicate that a previously unrecognized capsular population of hepatic stellate cells expands in response to fibrotic disease. Our findings reveal that various fibroblast subpopulations respond differently to pathological insults. This data resource will be relevant for the advancement of therapies targeting hepatic diseases.