Single Cell RNAseq analysis of mouse NASH liver cells

The liver is undergoing major rearrangements during the development of non-alcoholic steatohepatitis (NASH), from steatosis to severe lipid accumulation, inflammation and fibrosis. The mechanisms for this transition and the molecular changes preceding NASH are not fully understood. Here, we perform a single-cell RNA sequencing survey of 13,240 mouse liver cells during the development of non-alcoholic fatty liver disease. By measuring the entire transcriptome on a single-cell level from mice in the early stages of NASH development, we recognize known hepatocyte cell populations, Kupffer cells and stellate cells, as well as distinct gene expression changes in hepatocytes. We also reveal high hepatocyte heterogeneity in steatosis markers which projects a lipogenic trajectory of known and novel steatosis-associated genes. Importantly, we uncover distinct clusters of hepatocytes characterized by high or low Srebp1c expression with unique molecular signatures of lipogenesis. These results identify a novel regulatory pathway for lipogenesis in the liver that contributes to NASH progression. Overall design: we compared the gene expression profile at single-cell level of diet-induced NASH mouse liver against chow mouse liver.