Single-Cell Analysis of Fibroblast Subpopulations in Skin and Oral Mucosa

Fibroblasts are the principal mesenchymal cell type found within the connective tissues of all organs. Once thought to play a passive role in tissue remodeling, fibroblasts have now emerged as a key player in regulating structural immunity and modulating the reparative injury response. A recent surge in single-cell RNA sequencing studies has advanced our understanding of the biology of fibroblasts, highlighting their cellular diversity and organization across health and diseased conditions at an unprecedented resolution. In this review, we discuss up-to-date literature on fibroblast subpopulations identified from 2 distinct barrier tissues: oral mucosa and skin. We focus on the transcriptomic signatures that distinguish subsets of fibroblasts in homeostasis and perturbed conditions (i.e., wound healing or chronic inflammatory diseases), and we link them to mechanistic studies that provide functional insights. A deeper understanding of fibroblast diversity and its functional significance may uncover tissue-specific roles in regeneration and immunomodulation, which will be crucial for the development of precision therapy that directly targets fibroblast subsets.