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Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells

Neural crest cells (NC cells) are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network...

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Autores principales: Motohashi, Tsutomu, Watanabe, Natsuki, Nishioka, Masahiro, Nakatake, Yuhki, Yulan, Piao, Mochizuki, Hiromi, Kawamura, Yoshifumi, Ko, Minoru S. H., Goshima, Naoki, Kunisada, Takahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810742/
https://www.ncbi.nlm.nih.gov/pubmed/26873953
http://dx.doi.org/10.1242/bio.015735
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author Motohashi, Tsutomu
Watanabe, Natsuki
Nishioka, Masahiro
Nakatake, Yuhki
Yulan, Piao
Mochizuki, Hiromi
Kawamura, Yoshifumi
Ko, Minoru S. H.
Goshima, Naoki
Kunisada, Takahiro
author_facet Motohashi, Tsutomu
Watanabe, Natsuki
Nishioka, Masahiro
Nakatake, Yuhki
Yulan, Piao
Mochizuki, Hiromi
Kawamura, Yoshifumi
Ko, Minoru S. H.
Goshima, Naoki
Kunisada, Takahiro
author_sort Motohashi, Tsutomu
collection PubMed
description Neural crest cells (NC cells) are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs) into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+) cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells.
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spelling pubmed-48107422016-04-04 Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells Motohashi, Tsutomu Watanabe, Natsuki Nishioka, Masahiro Nakatake, Yuhki Yulan, Piao Mochizuki, Hiromi Kawamura, Yoshifumi Ko, Minoru S. H. Goshima, Naoki Kunisada, Takahiro Biol Open Research Article Neural crest cells (NC cells) are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES-Venus mouse embryonic fibroblasts (MEFs) into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+) cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells. The Company of Biologists Ltd 2016-02-12 /pmc/articles/PMC4810742/ /pubmed/26873953 http://dx.doi.org/10.1242/bio.015735 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Motohashi, Tsutomu
Watanabe, Natsuki
Nishioka, Masahiro
Nakatake, Yuhki
Yulan, Piao
Mochizuki, Hiromi
Kawamura, Yoshifumi
Ko, Minoru S. H.
Goshima, Naoki
Kunisada, Takahiro
Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
title Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
title_full Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
title_fullStr Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
title_full_unstemmed Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
title_short Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
title_sort gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810742/
https://www.ncbi.nlm.nih.gov/pubmed/26873953
http://dx.doi.org/10.1242/bio.015735
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