Dysfunction of hair follicle mesenchymal progenitors contributes to age related hair loss

Advanced age drives the progressive degeneration of mammalian hair follicles (HF) and termination of its regeneration cycle. The role of hair follicle dermal stem cell (hfDSC) in this age-associated HF dysfunction remains largely unexplored. Here, we first characterize a novel function of hfDSCs in regenerating the full dermal papilla (DP) after laser ablation. Next, we performed long-term fate mapping, age-dependant in vivo clonal analysis and in vitro proliferation assay on hfDSCs to describe the age-related defects in mesenchymal stem cell self-renewal and differentiation capabilities. Moreover, single-cell RNA-sequencing of the HF mesenchymal population mapped the intrinsic transcriptional changes that may drive their age-related dysfunction. We highlight the requirement of hfDSCs for normal HF regeneration. Our findings characterize a novel function of mesenchymal stem cells, and how this crucial cell becomes dysfunctional with age to drive age-related hair loss.