Fibroblast bioelectric signaling drives hair growth

Abstract

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 an inverted duplication 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 a reduction in intracellular calcium levels. Notably, fibroblast membrane potential oscillates during the 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.

Keywords: KCNJ2; bioelectric signaling; fibroblast niche; hair follicle regeneration.