Single Cell Transcriptomics Reveal Genomic Indicators of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) affects roughly 25% of people globally. This paper seeks to use single cell RNA sequencing (scRNA-seq) to identify genomic markers for the identification of NAFLD and the evaluation of therapeutic methods in silico. Publicly available scRNA-seq datasets of livers of both control and NAFLD mice were analyzed in R using the Seurat package for scRNA-seq analysis. Datasets were clustered as needed using the Seurat standard preprocessing workflow, and the zonation of hepatocyte clusters was identified based on established marker genes. When examining hepatocyte reprogramming during NAFLD, trends were seen in the zonation of hepatocytes expressing fructose metabolism pathways such as Aldob, Slc2a5 and Khk. In one dataset, healthy livers showed elevated expression of fructose metabolism pathways in central hepatocytes, while NAFLD livers exhibited this expression predominantly in portal hepatocytes. Conversely, in a second dataset, this zonation pattern was reversed, with central hepatocytes in NAFLD livers showing higher fructose metabolism expression compared to portal regions. This consistent observation of a zonation switch across datasets strengthens our understanding of hepatocyte reprogramming during NAFLD and fibrosis. Further, the direction of this switching may provide insights into fibrosis etiology, potentially reflecting differences in diet and metabolic stressors that contribute to fibrosis progression. It could also prove valuable in in silico evaluations of therapies for NAFLD by identifying liver fibrosis.