Discovering Heterogeneous Leukocytes Subsets Associated With Alcoholic Steatohepatitis by scRNAseq Analysis

Abstract

The precise identification of immune cell type responses to alcoholic steatohepatitis (ASH) at the single-cell level remains unresolved. Therefore, in this study, we analyzed heterogeneous immune leukocytes associated with ASH at the single-cell level using high-dimensional single-cell RNA sequencing in alcoholic liver disease (ALD)-induced and healthy control mice. A t-distributed stochastic neighbor embedding plot for dimensionality reduction and 2D visualization was used to visualize heterogeneous immune cell types. Moreover, singleR was used for automated cell annotation to identify the cell types and differentially expressed genes from each cell type and their subsets. We observed a decline in the population of B cells and their subsets, with up and downregulated genes signifying an innate proinflammatory response as an important indication of alcohol-induced liver fibrosis. Additionally, neutrophil deficiency in the alcohol-induced mouse group was associated with ASH. An increase in eosinophils diverts further complications in liver fibrosis, suggesting the functional heterogeneity of granulocyte subsets. Overall, our findings may assist in discovering potential ALD biomarker cell types that are significantly reduced by frequent alcohol exposure and enhance our understanding of the circulating immune leukocytes that lead to alcohol-induced liver fibrosis.