Characterization of a melanocyte progenitor population in human interfollicular epidermis

It is still unknown whether the human interfollicular epidermis harbors a reservoir of melanocyte precursor cells. Here, we clearly distinguish between three distinct types of melanocytes in human interfollicular epidermis: (1) cKit⁺CD90^-, (2) cKit⁺CD90⁺, and (3) cKit^-CD90⁺. Importantly, we identify the Kit tyrosine kinase receptor (cKit) as a marker expressed specifically in mature, melanin-producing melanocytes. Thus, both cKit⁺CD90^- and cKit⁺CD90⁺ cells represent polydendritic, pigmented mature melanocytes, whereas cKit^-CD90⁺ cells display bipolar, non-dendritic morphology with reduced melanin content. Additionally, using tissue-engineered pigmented dermo-epidermal skin substitutes (melDESSs), we reveal that the cKit expression also plays an important role during melanogenesis in melDESS in vivo. Interestingly, cKit^-CD90⁺ cells lack the expression of markers such as HMB45, TYR, and TRP1 in vitro and in vivo. However, they co-express neural-crest progenitor markers and demonstrate multilineage differentiation potential in vitro. Hence, we propose that cKit^-CD90⁺ cells constitute the precursor melanocyte reservoir in human interfollicular epidermis.