Generation of integration-free induced neural stem cells from mouse fibroblasts

Sung Min Kim, Jong Wan Kim, Tae Hwan Kwak, Sang Woong Park, Kee Pyo Kim, Hyunji Park, Kyung Tae Lim, Kyuree Kang, Jonghun Kim, Ji Hun Yang, Heonjong Han, In suk Lee, Jung Keun Hyun, Young Min Bae, Hans R. Schöler, Hoon Taek Lee, Dong Wook Han

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish
Pages (from-to)14199-14212
Number of pages14
JournalJournal of Biological Chemistry
Volume291
Issue number27
DOIs
Publication statusPublished - 2016 Jul 1

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Neural Stem Cells
Fibroblasts
Stem cells
Mutagenesis
Retroviridae
Transcriptome
Epigenomics
Gene expression
Tumors
Plasmids
Transcription Factors
Genes
Genome
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Kim, S. M., Kim, J. W., Kwak, T. H., Park, S. W., Kim, K. P., Park, H., ... Han, D. W. (2016). Generation of integration-free induced neural stem cells from mouse fibroblasts. Journal of Biological Chemistry, 291(27), 14199-14212. https://doi.org/10.1074/jbc.M115.713578
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. / Generation of integration-free induced neural stem cells from mouse fibroblasts. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 27. pp. 14199-14212.
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Kim, SM, Kim, JW, Kwak, TH, Park, SW, Kim, KP, Park, H, Lim, KT, Kang, K, Kim, J, Yang, JH, Han, H, Lee, IS, Hyun, JK, Bae, YM, Schöler, HR, Lee, HT & Han, DW 2016, 'Generation of integration-free induced neural stem cells from mouse fibroblasts', Journal of Biological Chemistry, vol. 291, no. 27, pp. 14199-14212. https://doi.org/10.1074/jbc.M115.713578

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 journalArticle

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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

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