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

Tsutomu Motohashi, Natsuki Watanabe, Masahiro Nishioka, Yuhki Nakatake, Piao Yulan, Hiromi Mochizuki, Yoshifumi Kawamura, Minoru S.H. Ko, Naoki Goshima, Takahiro Kunisada

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)311-322
Number of pages12
JournalBiology Open
Volume5
Issue number3
DOIs
Publication statusPublished - 2016 Mar 15

Keywords

  • Direct conversion
  • Mouse embryonic fibroblasts
  • Neural crest
  • Sox10

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Motohashi, T., Watanabe, N., Nishioka, M., Nakatake, Y., Yulan, P., Mochizuki, H., Kawamura, Y., Ko, M. S. H., Goshima, N., & Kunisada, T. (2016). Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells. Biology Open, 5(3), 311-322. https://doi.org/10.1242/bio.015735