Bulk RNA-seq and scRNA-seq analysis reveal an activation of immune response and compromise of secretory function in major salivary glands of obese mice

Comput Struct Biotechnol J. 2022 Dec 1:21:105-119. doi: 10.1016/j.csbj.2022.11.054. eCollection 2023.

Abstract

Obesity affects the function of multiple organs/tissues including the exocrine organ salivary glands. However, the effects of obesity on transcriptomes and cell compositions in the salivary glands have yet been studied by bulk RNA-sequencing and single-cell RNA-sequencing. Besides, the cell types in the sublingual gland, one of the three major salivary glands, have yet been characterized by the approach of single-cell RNA-sequencing. In this report, we find that the histological structure of the three major salivary glands are not obviously affected in the obese mice. Bulk RNA-sequencing analysis shows that the most prominent changes observed in the three major salivary glands of the obese mice are the mobilization of transcriptomes related to the immune response and down-regulation of genes related to the secretory function of the salivary glands. Based on single-cell RNA-sequencing analysis, we identify and annotate 17 cell clusters in the sublingual gland for the first time, and find that obesity alters the relative compositions of immune cells and secretory cells in the major glands of obese mice. Integrative analysis of the bulk RNA-sequencing and single-cell RNA-sequencing data confirms the activation of immune response genes and compromise of secretory function in the three major salivary glands of obese mice. Consequently, the secretion of extracellular matrix proteins is significantly reduced in the three major salivary glands of obese mice. These results provide new molecular insights into understanding the effect of obesity on salivary glands.

Keywords: High-fat diet; Obesity; RNA-seq; Salivary glands; scRNA-seq, mouse.