Characterization of cellular subpopulations and their gene expression by single-cell RNA sequencing in canine atopic dermatitis

Abstract

Abstract Atopic Dermatitis (AD) is the most common, chronic, and inflammatory allergic skin disease worldwide, with a high prevalence both in children and adults, particularly in developed countries. There are limited effective treatments for severe allergic skin diseases available, thus, there is an unmet need of better understanding the molecular mechanisms and cellular populations involved in AD. Since AD in canines closely resembles the disease in humans, they are an attractive animal model for further studies. Leveraging single-cell RNA sequencing, we identified the cellular composition and shifts in cell populations in canine epidermis of atopic dogs compared to the epidermis from healthy controls. Fibroblasts and keratinocytes represented the largest cell populations, with fibroblasts decreasing in the atopic epidermis. Other populations such as endothelial vascular cells showed differences as well. Shifts in immune cell distribution included changes in subpopulations of dendritic cells and monocytes in the atopic skin. NK and T cells, particularly CD8 T cells were increased. Subclustering revealed specific cellular changes in AD dogs. We found signifiant changes in gene expression in most cell populations, with some genes differentially expressed across cells, while others were expressed in a cell specific manner. We also observed subtle differences between samples from animals with different disease progression, identifying gene expression markers changing with AD severity. Here we show that single-cell sequencing is a useful tool to define the cellular composition in canine atopic dermatitis, resolving changes in gene expression at the cellular level to advance our understanding of disease development and progression. Supported by intramural funds from Western University of Health Sciences