Skin Fibroblast Heterogeneity and Plasticity Are Determined by the Local Niche

In 2019, a study was conducted on mouse dermal fibroblasts, which are derived from two distinct lineages and have unique roles in skin development, homeostasis, regeneration, and fibrosis. These fibroblasts showed differential expression of Wnt/β-catenin, Hedgehog and TGFβ pathway, and ECM components, and responded differently to signals from neoplastic epidermal cells. The study also found that the abundance, distribution, and expression profile of these fibroblast subsets changed with age and during the hair cycle, indicating high plasticity within the dermal mesenchyme. The researchers established a protocol for isolating distinct fibroblast subsets from human skin using fluorescence-activated cell sorting (FACS). They found that FAP+/CD90- cells, which are enriched in the upper dermis, showed increased proliferation and could not be differentiated into adipocytes, while FAP-/CD90+ and FAP+/CD90+ fibroblasts, which are derived from the reticular lineage, expressed high levels of ACTA2, MGP, PPARγ and CD36, and could readily undergo adipogenic differentiation. The study concluded that the microenvironment seems to affect the function of these fibroblasts, providing new tools to understand the functional heterogeneity and plasticity of fibroblast subsets in human skin pathogenesis.