Cell Type-Resolved Genomic Profiling of NASH and liver fibrosis

We generated hepatocyte-specific profiles of the genomic landscapes during NASH progression using the INTACT methodology We fed male HEP-INTACT mice two different NASH-inducing diets, 20 weeks of a FPC diet (Wang et al., 2016) or 7 weeks of a CDAHFD (Matsumoto et al., 2013), and control mice were fed a low fat diet for the same periods. Mice that had been fed NASH-inducing diets were divided into two groups, a mild and advanced NASH group, based on the liver histology. Whereas both groups had high levels of steatosis and inflammation compared to the control group, only the advanced NASH group displayed a significant degree of liver fibrosis. Livers were subsequently subjected to INTACT followed by ATAC-seq analyses.