Journal article
A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells
Biochemical and biophysical research communications, Vol.476(1), pp.42-48
07/15/2016
DOI: 10.1016/j.bbrc.2016.05.080
PMID: 27207831
Abstract
The generation of induced neural stem cells (iNSCs) from somatic cells using defined factors provides new avenues for basic research and cell therapies for various neurological diseases, such as Parkinson’s disease, Huntington’s disease, and spinal cord injuries. However, the transcription factors used for direct reprogramming have the potential to cause unexpected genetic modifications, which limits their potential application in cell therapies. Here, we show that a combination of four chemical compounds resulted in cells directly acquiring a NSC identity; we termed these cells chemically-induced NSCs (ciNSCs). ciNSCs expressed NSC markers (Pax6, PLZF, Nestin, Sox2, and Sox1) and resembled NSCs in terms of their morphology, self-renewal, gene expression profile, and electrophysiological function when differentiated into the neuronal lineage. Moreover, ciNSCs could differentiate into several types of mature neurons (dopaminergic, GABAergic, and cholinergic) as well as astrocytes and oligodendrocytes in vitro. Taken together, our results suggest that stably expandable and functional ciNSCs can be directly reprogrammed from mouse fibroblasts using a combination of small molecules without any genetic manipulation, and will provide a new source of cells for cellular replacement therapy of neurodegenerative diseases.
•A combination of small molecules enable MEFs direct reprogrammed into NSCs state.•ciNSCs express markers similar to NSCs and expanded in vitro for several passages.•ciNSCs have a potential to differentiate into the neural lineages in vitro.•ciNSCs differentiated into mature neurons have a multipotent differentiation.
Details
- Title: Subtitle
- A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells
- Creators
- Jie Zheng - Korea UniversityKyung-Ah Choi - Korea UniversityPhil Jun Kang - Korea UniversitySolji Hyeon - Korea UniversitySuhyun Kwon - Korea UniversityJai-Hee Moon - University of SeoulInsik Hwang - University of SeoulYang In Kim - Korea UniversityYoon Sik Kim - Korea UniversityByung Sun Yoon - Korea UniversityGyuman Park - Korea UniversityJangBo Lee - University of SeoulSungHoi Hong - Korea UniversitySeungkwon You - Korea University
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.476(1), pp.42-48
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bbrc.2016.05.080
- PMID
- 27207831
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Grant note
- name: Bio & Medical Technology Development Program; DOI: 10.13039/501100003725, name: National Research Foundation of Korea; name: Korean Ministry of Science, ICT & Future Planning, award: NRF-2010-0020347, NRF-2014M3A9D3034158, NRF-2012M3A9C6050131; name: Korea Health Technology R&D Project; name: Ministry of Health & Welfare, award: A120392, A12039212010000300; name: School of Life Sciences and Biotechnology
- Language
- English
- Date published
- 07/15/2016
- Academic Unit
- Neurosurgery
- Record Identifier
- 9984459621502771
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