MELANOCYTE PRECURSORS IN THE HAIR FOLLICLE BULGE OF REPIGMENTED VITILIGO SKIN ARE CONTROLLED BY RHO-GTPase, KCTD10 AND CTNNB1 SIGNALING

Abstract In repigmentation of human vitiligo, the melanocyte (MC) precursors in the hair follicle (HF) bulge proliferate, migrate and differentiate to repopulate the depigmented epidermis. Here we present a comprehensive characterization of pathways and signals in the bulge that control the repigmentation process. Using biopsies from vitiligo patients we have selectively harvested, by laser capture microdissection, MC and keratinocyte precursors from the HF bulge of untreated vitiligo skin and vitiligo skin treated with Narrow Band UVB (NBUVB). The captured material was subjected to whole transcriptome RNA sequencing. With this strategy, we found that repigmentation in the bulge MCs precursors is driven by KCTD10, a signal with unknown roles in the skin, and by CTNNB1 (encoding β-catenin) and RHO-GTPase (RHO), two signaling pathways previously shown to be involved in pigmentation biology. Knockdown studies in cultured human MCs of RHOJ, the upmost differentially expressed RHO component, corroborated with our findings in vitiligo patients, identified RHOJ involvement in UV response and melanization, and confirmed previously identified roles in melanocytic cell migration and apoptosis. A better understanding of mechanisms that govern repigmentation in the MCs precursors will enable discovery of molecules that induce robust repigmentation phenotypes in vitiligo.