Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency

Author:

Matsui Takeshi1,Takano Morito2,Yoshida Kenji1,Ono Soichiro1,Fujisaki Chikako1,Matsuzaki Yumi1,Toyama Yoshiaki2,Nakamura Masaya2,Okano Hideyuki1,Akamatsu Wado1

Affiliation:

1. Department of PhysiologyKeio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan

2. Department of Orthopedic Surgery, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan

Abstract

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. Disclosure of potential conflicts of interest is found at the end of this article.

Funder

Japan Society for the Promotion of Science

Japanese Ministry of Education, Culture, Sports, Science and Technology

Japan Science and Technology Agency

Keio Gijuku Academic Development Funds

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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