Study of human and mouse dermal fibroblast heterogeneity by single-cell RNA sequencing.

Abstract

The skin is a complex vital organ composed of several layers. The middle layer, the dermis, is mainly composed of fibroblasts that produce the extracellular matrix (ECM) providing structural support. Recent research using single-cell RNA sequencing (scRNAseq) has revealed previously unrecognized heterogeneity among dermal fibroblasts, challenging the traditional understanding of their organization.The work conducted in this thesis thoroughly analyses multiple human and mouse dermal scRNAseq datasets , uncovering a functional heterogeneity of fibroblasts never described. Fibroblast heterogeneity can be divided in major axes and minor populations, and more than 15 populations are described in each species. These populations were associated with specific functions, such as ECM production, immune response, involvement in skin adnexa such as hair follicles, or specialised supportive functions related to vasculature and nerve fibres. Additionally, while there are similarities between mouse and human fibroblasts, differences in their arrangement suggest species-specific variations in overall fibroblast function. This atlas serves as a valuable resource for researchers investigating skin function and diseases, enabling unbiased annotation of their datasets and facilitating the identification of compositional differences and novel fibroblast types associated with various skin conditions.