title: Neural stem cells directly differentiated from partially reprogrammed fibroblasts rapidly acquire gliogenic competency.
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.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsui
authors.forename: Morito
authors.initials: M
authors.lastname: Takano
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ono
authors.forename: Chikako
authors.initials: C
authors.lastname: Fujisaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D000090062:Kruppel-Like Factor 4; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology*