title: Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells.
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.
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0076, Japan tmotohas@gifu-u.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Motohashi
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishioka
authors.affiliation: Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA Department of Systems Medicine, Sakaguchi Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Nakatake
authors.affiliation: Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Piao
authors.initials: P
authors.lastname: Yulan
authors.affiliation: Japan Biological Informatics Consortium (JBiC), Tokyo 135-8073, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mochizuki
authors.affiliation: Japan Biological Informatics Consortium (JBiC), Tokyo 135-8073, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA Department of Systems Medicine, Sakaguchi Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Minoru S H
authors.initials: MS
authors.lastname: Ko
authors.affiliation: Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.affiliation: Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0076, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kunisada
keywords: Direct conversion; Mouse embryonic fibroblasts; Neural crest; Sox10