Figure 3.

Melanocyte stem cells (McSCs) and their responses to ultraviolet (UV) and stress. (A) Schematic of the melanocyte lineage during the hair cycle. Differentiated melanocytes are made during anagen to color the newly regenerated hair shaft. (B) UV irradiation leads to DNA damage in the epidermis and up-regulation of p53 and POMC (proopiomelanocortin), a precursor peptide that is processed to form β-endorphin, Adrenocorticotropic hormone (ACTH), and α-MSH (α-melanocyte-stimulating hormone). α-MSH binds to MC1R (melanocortin 1 receptor) to promote McSC migration toward the epidermis. MC1R signaling further up-regulates a transcription factor, MITF, which promotes melanocyte differentiation and melanin production. (EpdSC) Epidermal stem cells. (C) Under stress, sympathetic neurons become highly activated, releasing large amounts of norepinephrine (NE), which binds to the β2 adrenergic receptor (ADRB2) on McSCs to drive their hyperproliferation, differentiation, and permanent depletion.