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 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 patients with vitiligo, we have selectively harvested, by laser capture microdissection, MC and keratinocyte precursors from the hair follicle bulge of untreated vitiligo skin and vitiligo skin treated with narrow-band UVB. The captured material was subjected to whole transcriptome RNA-sequencing. With this strategy, we found that repigmentation in the bulge MC precursors is driven by KCTD10, a signal with unknown roles in the skin, and CTNNB1 (encoding β-catenin) and RHO guanosine triphosphatase [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 family component, corroborated with our findings in patients with vitiligo, 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 MC precursors will enable the discovery of molecules that induce robust repigmentation phenotypes in vitiligo.