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, Insuk Lee, Jung Keun Hyun, Young Min Bae, Hans R. Schöler, Hoon Taek Lee, Dong Wook Han

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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
Issue number27
Publication statusPublished - 2016 Jul 1

Bibliographical note

Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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