Generation of Integration-free Induced Neural Stem Cells from Mouse Fibroblasts.
J Biol Chem
; 291(27): 14199-14212, 2016 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-27189941
ABSTRACT
The viral vector-mediated overexpression of the defined transcription factors, Brn4/Pou3f4, Sox2, Klf4, and c-Myc (BSKM), could induce the direct conversion of somatic fibroblasts into induced neural stem cells (iNSCs). However, viral vectors may be randomly integrated into the host genome thereby increasing the risk for undesired genotoxicity, mutagenesis, and tumor formation. Here we describe the generation of integration-free iNSCs from mouse fibroblasts by non-viral episomal vectors containing BSKM. The episomal vector-derived iNSCs (e-iNSCs) closely resemble control NSCs, and iNSCs generated by retrovirus (r-iNSCs) in morphology, gene expression profile, epigenetic status, and self-renewal capacity. The e-iNSCs are functionally mature, as they could differentiate into all the neuronal cell types both in vitro and in vivo Our study provides a novel concept for generating functional iNSCs using a non-viral, non-integrating, plasmid-based system that could facilitate their biomedical applicability.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neurais
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article