Division of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, Japan.
Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.
Pigment Cell Melanoma Res. 2019 Sep;32(5):623-633. doi: 10.1111/pcmr.12779. Epub 2019 Mar 25.
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.
诱导多能干细胞（iPSC）技术为将人类原代成纤维细胞转化为黑素细胞提供了一种新方法。在尝试探索将 iPSC 分化为黑素细胞的各种方案时，我们发现了一种独特的、自我更新的细胞谱系，可分化为黑素细胞，称为黑素细胞前体细胞（MPC）。MPC 的形态与黑素细胞不同，既没有黑素小体结构，也没有黑素细胞特异性标记基因 MITF、TYR 和 SOX10。此外，MPC 的基因表达研究表明，高水平表达非经典 WNT 途径标记物 WNT5A 和 ROR2 及其相关受体 TGFβR2。相比之下，通过使用 GSK3β 抑制剂激活经典 WNT 途径，可实现 MPC 向黑素细胞的分化。我们的数据表明了 MPC 分化为黑素细胞的独特特征，以及经典 WNT 信号通路和非经典 WNT 信号通路之间的相互作用的潜在机制。
