Beyond the Epidermal-Melanin-Unit: The Human Scalp Anagen Hair Bulb Is Home to Multiple Melanocyte Subpopulations of Variable Melanogenic Capacity

Abstract

The visual appearance of humans is derived significantly from our skin and hair color. While melanin from epidermal melanocytes protects our skin from the damaging effects of ultraviolet radiation, the biological value of pigmentation in the hair follicle, particularly on the scalp, is less clear. In this study, we explore the heterogeneity of pigment cells in the human scalp anagen hair follicle bulb, a site conventionally viewed to be focused solely on pigment production for transfer to the hair shaft. Using c-KIT/CD117 microbeads, we isolated bulbar c-KIT-positive and c-KIT-negative melanocytes. While both subpopulations expressed MITF, only the c-KIT-positive fraction expressed SOX10. We further localized bulbar melanocyte subpopulations (expressing c-KIT, SOX10, MITF, and DCT) that exhibited distinct/variable expression of downstream differentiation-associated melanosome markers (e.g., gp100 and Melan-A). The localization of a second ‘immature’ SOX10 negative melanocyte population, which was c-KIT/MITF double-positive, was identified outside of the melanogenic zone in the most peripheral/proximal matrix. This study describes an approach to purifying human scalp anagen hair bulb melanocytes, allowing us to identify unexpected levels of melanocyte heterogeneity. The function of the more immature melanocytes in this part of the hair follicle remains to be elucidated. Could they be in-transit migratory cells ultimately destined to synthesize melanin, or could they contribute to the hair follicle in non-melanogenic ways?

A single-cell transcriptome atlas of Lueyang black-bone chicken skin

“…In the present study, scRNA-seq analysis revealed 12 candidate melanocyte markers, including NPY, GPNMB, SYP, TSPAN10, ROPN1L, CA2, GSTA3, SOX10, PTPN5, GSTO2, GSTA2 , and RAC2 . Among them, GPNMB ( Li et al, 2023b ), TSPAN10 ( Xi et al, 2020 ), ROPN1L ( Mazzio and Soliman, 2018 ), SOX10 ( Casalou et al, 2023 ), and RAC2 ( Liu et al, 2023 ) have been reported to be closely associated with melanin-related biological processes. They participate in the development of various diseases by influencing melanin-related physiological functions.…”

From Molecular Biology to Novel Immunotherapies and Nanomedicine in Uveal Melanoma

“…It should be emphasized that there were several attempts made to search for appropriate TAAs as targets in melanoma cells. Analyses comparing protein expression between skin and uvea melanomas indicate tumor antigens like tyrosinase, melan-A, and SOX10 [18,[85][86][87]. Another useful marker for distinguishing cell phenotypes (spindle from epithelioid) in skin melanomas, like p75NTR, is not appropriate in UM spindle cell identification.…”

“…However, unequivocal characteristics of cancer stem cells in UM are not confirmed. An additional difficulty in the identification of UM TAA antigens is the internal differentiation of tumor cells, as observed in cutaneous melanomas or hair follicles, where expression of the antigens characteristic of melanosomes changes together with the differentiated and undifferentiated states of these cells [87,94]. Despite the above difficulties, clinical trials using CAR-T therapy (NCT03635632) against inter alia uveal melanoma are ongoing.…”