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Generation of Human Melanocytes from Induced Pluripotent Stem Cells

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 differentiatio...

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Autores principales: Ohta, Shigeki, Imaizumi, Yoichi, Okada, Yohei, Akamatsu, Wado, Kuwahara, Reiko, Ohyama, Manabu, Amagai, Masayuki, Matsuzaki, Yumi, Yamanaka, Shinya, Okano, Hideyuki, Kawakami, Yutaka
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020956/
https://www.ncbi.nlm.nih.gov/pubmed/21249204
http://dx.doi.org/10.1371/journal.pone.0016182
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author Ohta, Shigeki
Imaizumi, Yoichi
Okada, Yohei
Akamatsu, Wado
Kuwahara, Reiko
Ohyama, Manabu
Amagai, Masayuki
Matsuzaki, Yumi
Yamanaka, Shinya
Okano, Hideyuki
Kawakami, Yutaka
author_facet Ohta, Shigeki
Imaizumi, Yoichi
Okada, Yohei
Akamatsu, Wado
Kuwahara, Reiko
Ohyama, Manabu
Amagai, Masayuki
Matsuzaki, Yumi
Yamanaka, Shinya
Okano, Hideyuki
Kawakami, Yutaka
author_sort Ohta, Shigeki
collection PubMed
description 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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spelling pubmed-30209562011-01-19 Generation of Human Melanocytes from Induced Pluripotent Stem Cells Ohta, Shigeki Imaizumi, Yoichi Okada, Yohei Akamatsu, Wado Kuwahara, Reiko Ohyama, Manabu Amagai, Masayuki Matsuzaki, Yumi Yamanaka, Shinya Okano, Hideyuki Kawakami, Yutaka PLoS One Research Article 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. Public Library of Science 2011-01-13 /pmc/articles/PMC3020956/ /pubmed/21249204 http://dx.doi.org/10.1371/journal.pone.0016182 Text en Ohta et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ohta, Shigeki
Imaizumi, Yoichi
Okada, Yohei
Akamatsu, Wado
Kuwahara, Reiko
Ohyama, Manabu
Amagai, Masayuki
Matsuzaki, Yumi
Yamanaka, Shinya
Okano, Hideyuki
Kawakami, Yutaka
Generation of Human Melanocytes from Induced Pluripotent Stem Cells
title Generation of Human Melanocytes from Induced Pluripotent Stem Cells
title_full Generation of Human Melanocytes from Induced Pluripotent Stem Cells
title_fullStr Generation of Human Melanocytes from Induced Pluripotent Stem Cells
title_full_unstemmed Generation of Human Melanocytes from Induced Pluripotent Stem Cells
title_short Generation of Human Melanocytes from Induced Pluripotent Stem Cells
title_sort generation of human melanocytes from induced pluripotent stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020956/
https://www.ncbi.nlm.nih.gov/pubmed/21249204
http://dx.doi.org/10.1371/journal.pone.0016182
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