Neural stem cells directly differentiated from partially reprogrammed fibroblasts rapidly acquire gliogenic competency

Takeshi Matsui, Morito Takano, Kenji Yoshida, Soichiro Ono, Chikako Fujisaki, Yumi Matsuzaki, Yoshiaki Toyama, Masaya Nakamura, Hideyuki Okano, Wado Akamatsu

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Neural stem cells (NSCs) were directly induced from mouse fibroblasts using four reprogramming factors (Oct4, Sox2, Klf4, and cMyc) without the clonal isolation of induced pluripotent stem cells (iPSCs). These NSCs gave rise to both neurons and glial cells even at early passages, while early NSCs derived from clonal embryonic stem cells (ESCs)/iPSCs differentiated mainly into neurons. Epidermal growth factor-dependent neurosphere cultivation efficiently propagated these gliogenic NSCs and eliminated residual pluripotent cells that could form teratomas in vivo. We concluded that these directly induced NSCs were derived from partially reprogrammed cells, because dissociated ESCs/iPSCs did not form neurospheres in this culture condition. These NSCs differentiated into both neurons and glial cells in vivo after being transplanted intracranially into mouse striatum. NSCs could also be directly induced from adult human fibroblasts. The direct differentiation of partially reprogrammed cells may be useful for rapidly preparing NSCs with a strongly reduced propensity for tumorigenesis.

Original languageEnglish
Pages (from-to)1109-1119
Number of pages11
JournalStem Cells
Volume30
Issue number6
DOIs
Publication statusPublished - 2012 Jun 1

Keywords

  • Direct cell conversion
  • Induced pluripotent stem cells
  • Neural induction
  • Neural stem cell
  • Reprogramming

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Matsui, T., Takano, M., Yoshida, K., Ono, S., Fujisaki, C., Matsuzaki, Y., Toyama, Y., Nakamura, M., Okano, H., & Akamatsu, W. (2012). Neural stem cells directly differentiated from partially reprogrammed fibroblasts rapidly acquire gliogenic competency. Stem Cells, 30(6), 1109-1119. https://doi.org/10.1002/stem.1091