Induced pluripotent stem cell‐derived melanocyte precursor cells undergoing differentiation into melanocytes

• Published in: Pigment cell and melanoma research 2019-09, Vol.32 (5), p.623-633
• Main Authors: Hosaka, Chieko, Kunisada, Makoto, Koyanagi‐Aoi, Michiyo, Masaki, Taro, Takemori, Chihiro, Taniguchi‐Ikeda, Mariko, Aoi, Takashi, Nishigori, Chikako
• Format: Article
• Language: English
• Subjects: Cell Differentiation; Cell Lineage; Cells, Cultured; Cytology; Differentiation; Embryos; Fibroblasts; Gene expression; Glycogen Synthase Kinase 3 beta - metabolism; human primary melanocytes; Humans; induced pluripotent stem cells; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Inhibitory postsynaptic potentials; melanocyte precursor cells; Melanocytes; Melanocytes - cytology; Melanocytes - metabolism; Microphthalmia-associated transcription factor; Morphology; Pluripotency; Precursors; Signal transduction; Signaling; Sox10 protein; Stem cells; Wnt protein; Wnt Proteins - metabolism; WNT signaling
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12779

Induced pluripotent stem cell (iPSC) technology offers a novel approach for conversion of human primary fibroblasts into melanocytes. During attempts to explore various protocols for differentiation of iPSCs into melanocytes, we found a distinct and self‐renewing cell lineage that could differentiate into melanocytes, named as melanocyte precursor cells (MPCs). The MPCs exhibited a morphology distinctive from that of melanocytes, in lacking either the melanosomal structure or the melanocyte‐specific marker genes MITF, TYR, and SOX10. In addition, gene expression studies in the MPCs showed high‐level expression of WNT5A, ROR2, which are non‐canonical WNT pathway markers, and its related receptor TGFβR2. In contrast, MPC differentiation into melanocytes was achieved by activating the canonical WNT pathway using the GSK3β inhibitor. Our data demonstrated the distinct characteristic of MPCs' ability to differentiate into melanocytes, and the underlying mechanism of interfacing between canonical WNT signaling pathway and non‐canonical WNT signaling pathway.