日本庆应义塾大学教授河上裕率领的研究小组近日在美国在线杂志《科学公共图书馆综合卷》上发表论文说，他们利用人体诱导多功能干细胞（iPS细胞），首次成功培养出色素细胞。

研究小组向人体皮肤细胞植入3个基因，培养生成诱导多功能干细胞，并培育出名为“胚状体（EB）”的细胞团块。接着，研究人员向胚状体植入人体制造色素细胞时所必需的成分，培育两个月左右，结果获得的细胞中有60％至70％是人体色素细胞。

色素细胞存在于人体皮肤等处，能够制造黑色素，防止人体遭受紫外线伤害。色素细胞如果出现癌变，就会患上恶性黑色素瘤等，而出现皮肤变白症状的白癜风和白化病以及白发等均被认为是色素细胞减少造成的。研究小组认为，新成果将有助于弄清上述疾病的致病原因，并且在制药和制作人造皮肤等再生医疗中得到应用。

推荐原文出处：

PLoS ONE 6(1): e16182. doi:10.1371/journal.pone.0016182

Generation of Human Melanocytes from Induced Pluripotent Stem Cells

Shigeki Ohta1#, Yoichi Imaizumi2#, Yohei Okada2,3, Wado Akamatsu2, Reiko Kuwahara1, Manabu Ohyama4, Masayuki Amagai4, Yumi Matsuzaki2, Shinya Yamanaka5,6, Hideyuki Okano2?*, Yutaka Kawakami1?*

1 Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan, 2 Department of Physiology, Keio University School of Medicine, Tokyo, Japan, 3 Kanrinmaru Project, Keio University School of Medicine, Tokyo, Japan, 4 Department of Dermatology, Keio University School of Medicine, Tokyo, Japan, 5 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan, 6 Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan

Abstract

Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma.

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