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 (eiNSCs) 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.
| Original language | English |
|---|---|
| Pages (from-to) | 14199-14212 |
| Number of pages | 14 |
| Journal | Journal of Biological Chemistry |
| Volume | 291 |
| Issue number | 27 |
| DOIs | |
| Publication status | Published - 2016 Jul 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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Generation of integration-free induced neural stem cells from mouse fibroblasts. / Kim, Sung Min; Kim, Jong Wan; Kwak, Tae Hwan; Park, Sang Woong; Kim, Kee Pyo; Park, Hyunji; Lim, Kyung Tae; Kang, Kyuree; Kim, Jonghun; Yang, Ji Hun; Han, Heonjong; Lee, In suk; Hyun, Jung Keun; Bae, Young Min; Schöler, Hans R.; Lee, Hoon Taek; Han, Dong Wook.
In: Journal of Biological Chemistry, Vol. 291, No. 27, 01.07.2016, p. 14199-14212.Research output: Contribution to journal › Article
TY - JOUR
T1 - Generation of integration-free induced neural stem cells from mouse fibroblasts
AU - Kim, Sung Min
AU - Kim, Jong Wan
AU - Kwak, Tae Hwan
AU - Park, Sang Woong
AU - Kim, Kee Pyo
AU - Park, Hyunji
AU - Lim, Kyung Tae
AU - Kang, Kyuree
AU - Kim, Jonghun
AU - Yang, Ji Hun
AU - Han, Heonjong
AU - Lee, In suk
AU - Hyun, Jung Keun
AU - Bae, Young Min
AU - Schöler, Hans R.
AU - Lee, Hoon Taek
AU - Han, Dong Wook
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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 (eiNSCs) 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.
AB - 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 (eiNSCs) 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.
UR - http://www.scopus.com/inward/record.url?scp=84976897352&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84976897352&partnerID=8YFLogxK
U2 - 10.1074/jbc.M115.713578
DO - 10.1074/jbc.M115.713578
M3 - Article
VL - 291
SP - 14199
EP - 14212
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 27
ER -