SPRY1 Deficiency in Keratinocytes Induces Follicular Melanocyte Stem Cell Migration to the Epidermis through p53/Stem Cell Factor/C-KIT Signaling

Abstract

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes. Keratinocytes and melanocytes respond to UV exposure by eliciting a tanning response. However, how keratinocytes and melanocytes interact in the absence of UV exposure is unknown. Here, we demonstrate that after SPRY1 knockout in epidermal keratinocytes, melanocyte stem cells (McSCs) in the hair follicle exit the niche without depleting the pool of these cells. We also found that McSCs migrate to the epidermis in a p53/SCF/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal keratinocytes. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of McSCs to the epidermis due to loss of SPRY1 in epidermal keratinocytes and show the potential for developing therapies for skin pigmentation disorders by manipulating McSCs.