Single-nucleus RNA-seq profiling of healthy and MASH mouse livers reveals hepatocyte heterogeneity under MASH condition

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe chronic liver condition characterized by hepatocyte steatosis, inflammation and fibrosis, with a rising prevalence globally, posing significant health risks and potentially leading to complications such as cirrhosis, liver failure, and increased mortality. To obtain a deeper understanding of transcriptomic responses to MASH diet feeding, we conducted a single-nucleus RNA-seq (snRNA-seq) experiment on livers from mice fed on regular chow or a MASH diet. Our snRNA-seq analysis revealed expansion of cholangiocytes and activated hepatic stellate cells population, as well as infiltration of macrophages in the MASH livers. In addition, we identified a cluster of hepatocytes, termed disease-associated hepatocytes, that are unique to the MASH livers and are distinct from the hepatocytes from the three liver zonations. Overall design: Wildtype C57BL6/J male mice were fed either on regular chow or with a MASH diet for five months. Liver tissues were collected for snRNA-seq experiment.