Phenotypic plasticity of melanocytes derived from human adult skin

Pigment Cell Melanoma Res. 2022 Jan;35(1):38-51. doi: 10.1111/pcmr.13012. Epub 2021 Aug 31.


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.

Keywords: dedifferentiation; melanocyte stem cells; melanocytes; melanoma; melanoma stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Dedifferentiation*
  • Cell Plasticity*
  • Cell Proliferation
  • Cells, Cultured
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Melanins / metabolism
  • Melanocytes / metabolism
  • Melanocytes / physiology*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Nestin / genetics
  • Nestin / metabolism
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • RNA-Seq
  • Signal Transduction
  • Skin / cytology*
  • Transcriptome
  • Young Adult


  • Melanins
  • Membrane Glycoproteins
  • NES protein, human
  • Nestin
  • Oxidoreductases
  • TYRP1 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit