Abstract
We previously described a novel in vitro culture technique for dedifferentiated human adult skin melanocytes. Melanocytes cultured in a defined, cholera toxin and PMA free medium became bipolar, unpigmented, and highly proliferative. Furthermore, TRP-1 and c-Kit expression disappeared and EGFR receptor and nestin expression were induced in the cells. Here, we further characterized the phenotype of these dedifferentiated cells and by comparing them to mature pigmented melanocytes we detected crucial steps in their phenotype change. Our data suggest that normal adult melanocytes easily dedifferentiate into pluripotent stem cells given the right environment. This dedifferentiation process described here for normal melanocyte is very similar to what has been described for melanoma cells, indicating that phenotype switching driven by environmental factors is a general characteristic of melanocytes that can occur independent of malignant transformation.
Highlights
Differentiated, pigment producing melanocytes are integral cellular components of human skin, and they are considered essential in UV protection
Pigment producing melanocytes are localized in the interfollicular epidermis surrounded by keratinocytes, while precursor melanoblasts are found in the hair follicle, and melanocyte lineage stem cells reside in the bulge area (Nishimura et al, 2002)
This plasticity depends on environmental or extrinsic factor mediated reprogramming of the cell and is referred to as extrinsic plasticity, as opposed to the intrinsic plasticity that is induced by forced expression of transcription factors (Gupta et al, 2019)
Summary
Pigment producing melanocytes are integral cellular components of human skin, and they are considered essential in UV protection. They differentiate from the neural crest, and the master transcriptional regulator in its full differentiation is the microphthalmia-associated transcription factor (MITF). C-Kit and TRP-1 expression disappeared, and nestin and epidermal growth factor receptor (EGFR) expression was induced in the cells. These cells could be passaged up to 15 passages before they reached complete senescence (Szabad et al, 2007). Our cultured cells represent a good system to investigate melanocyte phenotypic plasticity; in this work, we aimed to further characterize these in vitro dedifferentiated melanocytes and to detect intrinsic mechanisms governing cellular dedifferentiation by comparing the dedifferentiated cells to conventionally cultured pigment producing melanocytes using RNAseq
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