日本慶應義塾大學教授河上裕率領的研究小組近日在美國在線雜志《科學公共圖書館綜合卷》上發表論文說，他們利用人體誘導多功能干細胞（iPS細胞），首次成功培養出色素細胞。

研究小組向人體皮膚細胞植入3個基因，培養生成誘導多功能干細胞，并培育出名為“胚狀體（EB）”的細胞團塊。接著，研究人員向胚狀體植入人體制造色素細胞時所必需的成分，培育兩個月左右，結果獲得的細胞中有60％至70％是人體色素細胞。

色素細胞存在于人體皮膚等處，能夠制造黑色素，防止人體遭受紫外線傷害。色素細胞如果出現癌變，就會患上惡性黑色素瘤等，而出現皮膚變白癥狀的白癜風和白化病以及白發等均被認為是色素細胞減少造成的。研究小組認為，新成果將有助于弄清上述疾病的致病原因，并且在制藥和制作人造皮膚等再生醫療中得到應用。

推薦原文出處：

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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