title: Direct Conversion of Human Fibroblasts into Neural Progenitors Using Transcription Factors Enriched in Human ESC-Derived Neural Progenitors.
abstract: Early human embryonic stem cell (hESC)-derived neural populations consist of various embryonic neural progenitors (ENPs) with broad neural developmental propensity. Here, we sought to directly convert human somatic cells into ENP-like phenotypes using hESC-ENP-enriched neural transcription factors (TFs). We demonstrated that induced ENP could be efficiently converted from human fibroblasts using two TF combinations. The iENPs exhibit cellular and molecular characteristics resembling hESC-ENPs and can give rise to astrocytes, oligodendrocytes, and functional neuronal subtypes of the central and peripheral nervous system. Nevertheless, our analyses further revealed that these two iENP populations differ in terms of their proliferation ability and neuronal propensity. Finally, we demonstrated that the iENPs can be induced from fibroblasts from patients with Huntington's disease and Alzheimer's disease, and the diseased iENPs and their neuronal derivatives recapitulated the hallmark pathological features of the diseases. Collectively, our results point toward a promising strategy for generating iENPs from somatic cells for disease modeling and future clinical intervention.
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Hou
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan; Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Chuang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan.
authors.forename: Chan-Hsien
authors.initials: CH
authors.lastname: Yeh
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan.
authors.forename: Wei
authors.initials: W
authors.lastname: Chiang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan.
authors.forename: Hsiao-Jung
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Teng-Nan
authors.initials: TN
authors.lastname: Lin
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan; Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan. Electronic address: kuohuch@gate.sinica.edu.tw.
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D054338:Cell Transdifferentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons; D051381:Rats; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: cell fate conversion; disease modeling; induced neural progenitors; transcription factors