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.

Characterization of a melanocyte progenitor population in human interfollicular epidermis - Medicine Innovates
Figure 1. Distribution pattern of cKit/HMB45 and CD90 in the human interfollicular epidermis
(A and B) Confocal microscopic pictures of normal human foreskin revealed the presence of distinct cell populations in the basal cell layer of the epidermis: cKit- or HMB45-only positive cells (asterisks) as well as cells double-positive for cKit/HMB45 and CD90 (arrows). Insets represent the higher magnification of respective cKit/HMB45 and CD90 double-positive cells.
(C and D) Confocal microscopic pictures of normal human skin showed also the presence of single CD90+ cells in the basal cell layer of epidermis (arrowheads). Insets represent the higher magnification of respective CD90+ but cKit–/HMB45− cells. Lam5 highlights the dermo-epidermal junction. Images are representative of 6 independent biological donors (n = 6). Scale bars: 20 μm. E, epidermis; D, dermis.
(E) Quantification of cKit+CD90–, cKit+CD90+, and cKit–CD90+ melanocytes in the human foreskin samples. Data are presented as a mean ± SD (error bars) (n = 6). p values were calculated using unpaired two-tailed Student’s t test. ∗∗∗∗p < 0.0001, ns, not significant.

About the author

Dr. Agnes Klar is a Group Leader in the Tissue Biology Research Unit at the University Children’s Hospital Zurich, Switzerland. Agnes Klar received her Master’s Degree in Biological Sciences from the University of Konstanz in Germany and completed her PhD and habilitation at the University of Zurich. Her research focuses on human skin biology, skin pigmentation, inflammation, and wound healing in vitro and in vivo. Agnes Klar studies adult stem cells and their niches in adult and fetal human skin. In particular, Agnes investigates cellular and molecular mechanism regulating cell-cell interactions in skin wound healing, inflammation, and skin scarring. The overall aim of her research is to advance our understanding of tissue regeneration, to develop novel therapeutic options for the treatment of skin defects.

About the author

Dr. Katarzyna Michalak-Mićka is a postdoctoral researcher in the in the Tissue Biology Research Unit at the University Children’s Hospital Zurich, Switzerland. Dr. Micka received her Master Degree at the Cracow University of Technology in Poland and graduated with a PhD in biology from the University of Zurich. Her research studies focus on tissue engineering of cartilage applying stem cells derived from amniotic fluid samples for the in utero repair of spina bifida defect. Her goal is to develop an optimized method to produce mechanically stable cartilage graft containing cells and different biostructures in a preferably biocompatible, biodegradable matrix for clinical use in humans.

About the author

Dr. Thomas Biedermann is Head of the Tissue Biology Research Unit at the Dept. of Surgery of the University Children’s Hospital in Zurich, Switzerland. Dr. Biedermann obtained his Master’s Degree in Chemistry from the University of Leipzig, German, and received his PhD and habilitation at the University of Zurich. Dr. Biedermann is principle investigator in tissue engineering focusing on human skin substitutes. The research of Thomas Biedermann focuses on tissue engineering of human dermo-epidermal skin substitutes for clinical application for large skin lesions such as large burns. One main objective is thereby to bio-engineer prevascularized and pigmented skin substitutes that inoculate after transplantation to ensure fast blood circulation in the substitute and to eventually result in the patients’ physiological skin color.


Michalak-Mićka K, Büchler VL, Zapiórkowska-Blumer N, Biedermann T, Klar AS. Characterization of a melanocyte progenitor population in human interfollicular epidermis. Cell Reports. 2022 ;38(9):110419.

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