Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis.

ABSTRACT: Hepatocellular carcinoma (HCC), the fourth leading cause of cancer mortality worldwide, develops almost exclusively in patients with chronic liver disease and advanced fibrosis^1,2. Here we interrogated functions of hepatic stellate cells (HSCs), the main source of liver fibroblasts³, during hepatocarcinogenesis. Genetic depletion, activation or inhibition of HSCs in mouse models of HCC revealed their overall tumour-promoting role. HSCs were enriched in the preneoplastic environment, where they closely interacted with hepatocytes and modulated hepatocarcinogenesis by regulating hepatocyte proliferation and death. Analyses of mouse and human HSC subpopulations by single-cell RNA sequencing together with genetic ablation of subpopulation-enriched mediators revealed dual

SUBMITTER: Filliol A 

PROVIDER: S-EPMC9949942 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature