Melanocyte precursors in the hair follicle bulge of repigmented vitiligo skin are controlled by RHO-GTPase, KCTD10 and CTNNB1 signaling

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. 1)Gene expression profiles of hair follicle bulge melanocyte precursor samples (MCBG) from 6 vitiligo patients undergoing active NBUVB treatment were compared to gene expression profiles of hair follicle bulge melanocyte precursor samples (MCBG) from 6 untreated vitiligo patients; 2)Gene expression profiles of hair follicle bulge outer root sheath keratinocyte samples (KCBG) from 6 vitiligo patients undergoing active NBUVB treatment were compared to gene expression profiles of hair follicle bulge outer root sheath keratinocyte samples (KCBG) from 6 untreated vitiligo patients. Both comparisons utilized F-LCM on full-thickness skin biopsies. 100 captured cells were pooled for each sample, RNA was extracted, amplified, and subjected to whole transcriptome RNA-Seq.