Hair follicle melanocyte precursors are awoken by ultraviolet radiation via a cell extrinsic mechanism

Abstract

Melanocyte stem cells (MCSCs) in the upper portion of the hair follicle periodically supply melanocytes (MCs) that migrate downward into the hair bulb during anagen, the growth phase of the hair cycle. However MCs can also migrate upwards. We previously observed an increase in epidermal MC density in the mouse epidermis after a single ultraviolet radiation (UVR) exposure in neonatal, but not adult mice. To better understand MCSC activation by UVR we methodically studied the response of MCs to narrow band UVB (since UVA does not invoke this response) exposure in neonatal mice, and in adults at different stages of the hair cycle. We found that a single exposure of adult mice did not induce activation of MCSCs, in any stage of the hair cycle. When adult mice MCSCs were isolated in telogen, multiple UVB exposures resulted in their activation and production of daughter cells, which migrated upwards to the epidermis. Importantly, the MCSCs produced new progeny without themselves having incurred DNA damage after UVB exposure. This, together with examination of MC localisation in the skin of mice overexpressing stem cell factor in their keratinocytes, leads us to conclude that MCSC activation by UVB is driven via paracrine production of either SCF and/or other keratinocyte cytokines. We re-examined the increase in epidermal MC density in neonatal mouse skin. This effect was much more profound after only a single exposure than that of even multiple exposures to adult skin, and we show that in this setting also, the epidermal MCs mostly derive from activation of MC precursors in the upper hair follicle, and most likely via a cell extrinsic mechanism. Hence, although adaptive changes in the skin induced by repetitive UVB exposures are necessary in adult mice, in both the adult and neonatal context the division and migration upwards of follicular MCSCs is the major mode by which epidermal MC numbers increase after UVR exposure.