Single-nucleus RNA-seq profiling of mouse livers with hepatocyte-specific ablation of Themis under MASH diet feeding

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. Previous study in our lab has identified Themis as a highly up-regulated gene in hepatocytes during MASH progression using a diet-induced mouse model. To gain further insights into the roles of Themis in regulating hepatic responses to MASH diet, we generated mice with hepatocyte-specific ablation of Themis (HKO). The HKO mice exhibited worse MASH symptoms, including more severe steatosis, liver injury, fibrosis and more immune cell infiltration, relative to their Themis flox/flox control littermates. Overall design: C57BL6/J mice with hepatocytes-specific ablation of Themis (HKO) were established by crossing Themis flox/flox mice with a line carrying Albumin promoter-driven Cre (Alb-Cre). Male mice were fed on a MASH diet for five months. Liver tissues were collected for snRNA-seq experiment.