Generation of Integration-free Induced Neural Stem Cells from Mouse Fibroblasts*
| Autor: | Hoon Taek Lee, Jung Keun Hyun, Tae Hwan Kwak, Young Min Bae, Hans R. Schöler, Jonghun Kim, Sung Min Kim, Kee-Pyo Kim, Insuk Lee, Kyung Tae Lim, Sang Woong Park, Heonjong Han, Jong-Wan Kim, Ji Hun Yang, Dong Wook Han, Kyu-Ree Kang, Hyun Ji Park |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Somatic cell Genetic Vectors Transfection Biochemistry Viral vector 03 medical and health sciences Kruppel-Like Factor 4 Mice Retrovirus SOX2 Neural Stem Cells Animals Molecular Biology Mice Inbred C3H biology Cell Biology Fibroblasts biology.organism_classification Molecular biology Neural stem cell Cell biology 030104 developmental biology KLF4 Reprogramming |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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