title: Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules.
abstract: Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytes in vitro and in vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical medicine.
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia; Department of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, P.O. Box 2100, Adelaide, SA 5001, Australia.
authors.forename: Yan-Chuang
authors.initials: YC
authors.lastname: Han
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, P.O. Box 2100, Adelaide, SA 5001, Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Duffieldl
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Nimshitha Pavathuparambil
authors.initials: NP
authors.lastname: Abdul Manaph
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Miao
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, P.O. Box 2100, Adelaide, SA 5001, Australia.
authors.forename: Damien J
authors.initials: DJ
authors.lastname: Keating
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia; Department of Human Physiology and Centre for Neuroscience, Flinders University of South Australia, P.O. Box 2100, Adelaide, SA 5001, Australia.
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Zhou