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

  • Tsutomu Motohashi
    Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
  • Natsuki Watanabe
    Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
  • Masahiro Nishioka
    Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
  • Yuhki Nakatake
    Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA
  • Piao Yulan
    Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA
  • Hiromi Mochizuki
    Japan Biological Informatics Consortium (JBiC), Tokyo 135-8073, Japan
  • Yoshifumi Kawamura
    Japan Biological Informatics Consortium (JBiC), Tokyo 135-8073, Japan
  • Minoru S. H. Ko
    Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA
  • Naoki Goshima
    Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan
  • Takahiro Kunisada
    Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan

Description

<jats:title>ABSTRACT</jats:title><jats:p>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.</jats:p>

Journal

  • Biology Open

    Biology Open 5 (3), 311-322, 2016-02-12

    The Company of Biologists

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