Fibroblast bioelectric signaling drives hair growth (PRJCA041587)
Hair loss affects millions globally, significantly impacting quality of life and psychological well-being. Despite its prevalence, effective strategies for promoting human hair growth remain elusive. By investigating Congenital Generalized Hypertrichosis Terminalis (CGHT), a rare genetic disorder characterized by excessive hair growth, we discover that chromatin deletions or duplicate inversion disrupt the topologically associating domain (TAD), leading to the upregulation of the potassium channel KCNJ2 in dermal fibroblasts. Mouse genetics demonstrate that KCNJ2-mediated membrane hyperpolarization in dermal fibroblasts promotes hair growth by enhancing fibroblasts Wnt signaling responses, involving reduction in intracellular calcium levels. Notably, fibroblast membrane potential oscillates during normal hair cycle, with hyperpolarization specifically associated with the growth phase. Inducing fibroblast membrane depolarization delays the growth phase, while KCNJ2-mediated hyperpolarization rescues hair loss in aging and androgenetic alopecia models. These results uncover a previously unrecognized role of fibroblast bioelectricity in tissue regeneration, offering novel therapeutic avenues for hair loss treatment.