title: Generation of integration-free and region-specific neural progenitors from primate fibroblasts.
abstract: Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hr, then they were cultured in a chemically defined medium containing leukemia inhibitory factor (LIF), transforming growth factor (TGF)-β inhibitor SB431542, and glycogen synthase kinase (GSK)-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP) colonies appeared as early as day 13 and can be expanded for >20 passages. Under the same defined condition, no induced pluripotent stem cell (iPSC) colonies formed at either 37°C or 39°C. The iNPs predominantly express hindbrain genes and differentiate into hindbrain neurons, and when caudalized, they produced an enriched population of spinal motor neurons. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. The ability to generate defined, integration-free iNPs from adult primate fibroblasts under a defined condition with predictable fate choices will facilitate disease modeling and therapeutic development.
authors: Department of Neuroscience, School of Medicine and Public Health, Waisman Center, University of Wisconsin, Madison, Madison, WI 53705, USA.
authors: Jianfeng
authors: J
authors: Lu
authors: Huisheng
authors: H
authors: Liu
authors: Cindy Tzu-Ling
authors: CT
authors: Huang
authors: Hong
authors: H
authors: Chen
authors: Zhongwei
authors: Z
authors: Du
authors: Yan
authors: Y
authors: Liu
authors: Mohammad Amin
authors: MA
authors: Sherafat
authors: Su-Chun
authors: SC
authors: Zhang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation; D004149:Dioxoles / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D000882:Haplorhini; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D058953:Neural Stem Cells / Q000166:cytology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012249:Rhombencephalon / Q000378:metabolism; D013696:Temperature
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; C473711:Chir 99021; D004149:Dioxoles; D053605:Leukemia Inhibitory Factor; D011725:Pyridines; D011743:Pyrimidines
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