Genome-wide open chromatin analysis of liver sinusoidal endothelial cells in the pathogenesis of NASH

We isolated liver sinusoidal endothelial cells (LSEC) from mice fed control chow (Chow) or the nonalcoholic steatohepatitis (NASH)-inducing high fat, fructose and cholesterol (FFC) diet, and subjected the cells to Omni-ATAC-seq. Out of the top 500 differentially abundant open chromatin regions between the two groups, 498 were more robust in FFC-fed mice compared with Chow-fed mice, suggesting a genome-wide active epigenetic regulation in LSEC during NASH development. Furthermore, in combination with RNA-seq, we demonstrated a robust transcriptional upregulation of the adhesion molecule VCAM-1 in LSEC in NASH pathogenesis. Overall design: Liver sinusodial endothelial cells from NASH and control mice were subjected to Omni-ATAC-seq analysis.