Characterization of a melanocyte progenitor population in human interfollicular epidermis

The basal cell layer contains dendritic pigment-producing cells called melanocytes. Although all melanocytes have the ability to synthesize melanin and originate from same embryonic cells known as neural crest cells (NCC), their individual roles in each target location go much beyond just producing melanin. The embryonic progenitors of the pigment-producing melanocytes found in the skin, meninges, heart, and ears are called melanoblasts. Melanocytes’ life cycle involves various steps comprising lineage specification from embryonic neural crest cells, migration and proliferation of melanoblasts, differentiation of melanoblasts into melanocytes, their maturation, transport of mature melanosomes to keratinocytes, and eventual cell death. While hair melanocytes pass away at the end of the 3–8 year long hair cycle, epidermal melanocytes have a long lifespan.

Some studies have shown the possibility and prospects of mesenchymal stem cells used in tissue engineering skin. The establishment of tissue-engineered skin could solve the problems of cells, scaffolds, and growth stimulation signals. The human hair bulge contains melanoblasts, which have been defined as the amelanotic precursor cells of melanocytes. They serve as a source of stem cells for the periodic hair cycle. They may develop first from neural crest cells or secondarily from Schwann cell precursors, another type of NCC-derived cell. Previous published reports reveal that there is a major difference in functional characteristics of melanocytes between mice and human. One significant distinction is that in mice, amelanotic melanoblasts are seen not only in the hair bulge but also in the epidermis (non-hairy part). This prompts the question of whether the interfollicular epidermis of humans also has a population of amelanotic melanoblasts that would serve as a comparable source of stem cells.

In a new study conducted by Swiss scientists at the University Children’s Hospital Zurich, University of Zurich: Dr. Katarzyna Michalak-Micka, Dr. Vanessa Buchler, Natalia Zapiorkowska-Blumer, PD Dr. Thomas Biedermann and PD Dr. Agnes S. Klar conducted elegant molecular and cellular studies to characterize melanocyte subpopulations in the interfollicular human epidermis. The research team  looked at whether the interfollicular epidermis of humans  contains populations of mature and precursor melanocytes. Authors performed confocal imaging of triple immunofluorescence co-staining for cKit, CD90, HMB45 and Laminin 5 to image mature and progenitor melanocytes in the epidermal basement membrane. Knowledge of melanocyte population homoeostasis and its recovery after injury significantly depends on the accurate identification and detailed characterization of the many melanocyte cell groups. The current investigation found three distinct kinds of melanocytes subpopulations in the human interfollicular epidermis: cKit⁺CD90^–, cKit⁺CD90⁺, and cKitCD90⁺. The discovery of the Kit tyrosine kinase receptor (cKit) as a marker uniquely expressed in mature, melanin-producing melanocytes is noteworthy. The research work is now published in the journal Cell Reports.

The researchers showed that only cKitCD90⁺ cells are melanocyte progenitor cells, whereas cKit⁺CD90^– cells are pigmented melanocytes that have undergone full differentiation. Additional in vivo studies using pigmented dermo-epidermal replacements demonstrated that melanocyte cKit expression is crucial for the pigmentation of skin grafts in vivo (melDESSs). They observed that while cKit⁺CD90^– melanocytes had the maximum degree of melanin expression, cKit⁺CD90⁺ cells had a moderate quantity of melanin, and cKitCD90⁺ cells barely produced any melanin pigment in the corresponding melDESSs. According to recent findings, cKit signaling is necessary for the differentiation of human interfollicular melanocytes.

In conclusion, these findings provide critical insights into the variety of melanocytes in the human interfollicular epidermis and their capacity for differentiation. The authors claim that the interfollicular epidermis of humans has a pool of progenitor melanocytes made up of cKitCD90⁺ cells. In the typical human skin, authors successfully differentiated between cKit⁺CD90^–, cKit⁺CD90⁺, and cKitCD90⁺ melanocyte subpopulations

Skin grafting is one of the most promising approaches to heal extensive wounds. The discoveries of the Swiss scientists also enable skin-tone customization, making it a significant advancement in the therapeutic application of pigmented human bio-engineered skin grafts.

Moreover, the findings of this study could pave the way for new treatment methods for severe skin disease including vitiligo, postinflammatory hypopigmentation, albinism, piebaldism, melasm, hypomelanosis, and café-au-lait macules.