title: A combination of small molecules directly reprograms mouse fibroblasts into neural stem cells.
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.
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-701, Republic of Korea; Department of Chemistry, College of Science, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Choi
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Phil Jun
authors.initials: PJ
authors.lastname: Kang
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Solji
authors.initials: S
authors.lastname: Hyeon
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Suhyun
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Jai-Hee
authors.initials: JH
authors.lastname: Moon
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Insik
authors.initials: I
authors.lastname: Hwang
authors.affiliation: Department of Physiology, College of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Yang In
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Korea University, Seoul 136-705, Republic of Korea.
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea; StemLab, Venture Incubation Center, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Yoon
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Gyuman
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: JangBo
authors.initials: J
authors.lastname: Lee
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul 136-701, Republic of Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: shong21@korea.ac.kr.
authors.forename: SungHoi
authors.initials: S
authors.lastname: Hong
authors.affiliation: Laboratory of Cell Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: bioseung@korea.ac.kr.
authors.forename: Seungkwon
authors.initials: S
authors.lastname: You
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming / Q000187:drug effects*; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D054852:Small Molecule Libraries / Q000378:metabolism
chemical_list: D054852:Small Molecule Libraries
keywords: Lineage conversion; Neural stem cell; Reprogramming; Small molecules