KIT Expression Reveals a Population of Precursor Melanocytes in Human Skin

Abstract

Human skin is believed to harbor a reservoir population of precursor melanocytes. It has been difficult to identify these putative cells experimentally, because they lack phenotypic features that define mature melanocytes. We have evaluated expression of the KIT tyrosine kinase receptor, which is critical for melanocyte development, as a possible marker of these cells. Sections of human skin were evaluated with single- and double-immunolabeling techniques. KIT-reactive dendritic cells were identified in the basal layer of the epithelia and were most numerous in the follicular infundibula and the rete ridges. These cells were located on the epithelial side of the basement membrane and lacked expression of cytokeratin and mast cell tryptase. The location of the KIT-reactive cells was distinctly different from that of Langerhans cells (identified with anti-CD1a) or Merkel cells (identified with CAM 5.2). Within the epidermis and upper follicular infundibulum the majority of the KIT-reactive dendritic cells also coexpressed TRP-1, a marker present in differentiated melanocytes. In the deeper follicular regions, the coexpression of TRP-1 in the KIT-reactive cells was absent. Throughout the epidermis and follicle, however, the KIT-reactive cells coexpressed BCL-2, a marker known to be increased in melanocytes. Thus, KIT expression reveals a population of intraepithelial cells that have immunophenotypic characteristics of mature melanocytes within the upper epithelial regions, but lack the differentiated melanocytic phenotype within the deeper follicular regions. We propose that these KIT(+), BCL-2(+), and TRP-1(-) cells constitute a precursor melanocyte reservoir of human skin.

Stem Cell Factor Combined with Matrix Proteins Regulates the Attachment and Migration of Melanocyte Precursors of Human Hair Follicles <i>in Vitro</i>

“…9) Thus, FN, LN and CIV are tightly adjacent to each other, with MPs localized in the deeper follicular regions, where KIT is expressed on the surface of MPs. 13,14) Therefore, it is likely that the chemotaxis and attachment of MPs regulated by SCF combined with matrix proteins in vitro shares similar characteristics as MPs migration from the ORS into the epidermis, although the environment is more complicated in vivo. The decreased attachment of MPs to FN and CIV caused by SCF most likely facili- tated the migration of MPs along the basement membrane of the ORS, and the chemotactic effects of SCF combined with FN supplied a driving force for MPs migration.…”

“…Within the deeper follicular ORS, the population of precursor melanocytes expresses only KIT and lacks the differentiated melanocytic phenotype. 13,14) As the exclusive ligand of KIT, stem cell factor (SCF) can increase melanocytes proliferation, differentiation, survival, chemotaxis and accumulation in vivo. 15,16) The major role of SCF in melanogenic phenomena has been thought to be targeting KIT-bearing melanoblasts or melanocytes, as evidenced by the migration of immature melanocytes from the neural crest toward the hair follicles via the epidermis.…”

Molecular and cellular pathogenesis of melanoma initiation and progression

“…Cancer stem cells (CSCs) are thought to be implicated in melanoma tumour initiation, progression, chemoresistance and recurrence in human malignant melanoma [78][79][80][81][82].…”

Feeder-free Derivation of Melanocytes from Human Pluripotent Stem Cells

“…Human melanoblasts migrate to the basal layer of the epidermis where they reside either in the hair bulge or surrounded by keratinocytes in the epidermis (forming pigmentation units) to serve as precursors to the mature, pigmented melanocytes. The differentiation and maturation of melanoblasts into pigmented melanocytes occurs concomitant with colonization of the hair bulb and expression of the melanin production pathway (TYRP1, TYR, OCA2 and PMEL) 25,26 .…”