Deconvolution of cell types from bulk gene expression profiling in a nonalcoholic steatohepatitis model of mice liver reveals global alteration of macrophages and hepatic stellate cells

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease due to the accumulation of excess fat in the liver cells. The two histological categories of NAFLD are NASH (nonalcoholic steatohepatitis) and NAFL (nonalcoholic fatty liver). While NASH is typically considered a disorder of the hepatocytes, the role of other liver cell types in its pathophysiology and progression is becoming more established. Bioinformatics analytic approaches can now incorporate single cell RNA transcriptomics (sc-RNA-Seq) as a reference to deconvolute cell type profiles and proportions in bulk /RNA-Seq data. This technique can be inferred to investigate the changes in cellular compositions in tissues across multiple disease states. This study performed deconvolution analysis using CIBERSORTx, by integrating the bulk/RNA-Seq data with single-cell transcriptomic data to identify changes in cell composition associated with NASH. This study aimed to observe the changes in cell types among healthy and NASH mouse liver. The result of the analyses revealed a general increase in the fraction of HSC (Hepatic Stellate cells), liver macrophages, and cholangiocytes in NASH samples. Hepatocytes had a higher proportion in healthy samples compared with NASH, however, no significant observable difference was established in the endothelial cell proportions. We gained insight on the cell-type proportions profiles of NASH mice models, which highly mimics the human NASH.