title: Transcription factor induction of human oligodendrocyte progenitor fate and differentiation.
abstract: Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a(+)O4(+) OPCs relative to CD133(+)CD140a(-) neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs.
authors: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
authors: Jing
authors: J
authors: Wang
authors: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
authors: Suyog U
authors: SU
authors: Pol
authors: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
authors: Alexa K
authors: AK
authors: Haberman
authors: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
authors: Chunming
authors: C
authors: Wang
authors: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
authors: Melanie A
authors: MA
authors: O'Bara
authors: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214 fjsim@buffalo.edu.
authors: Fraser J
authors: FJ
authors: Sim
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D064593:Heterografts; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D016086:Lentivirus; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D014161:Transduction, Genetic
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715631:NKX2-2 protein, human; C000715627:Nkx2-2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: neural precursor cell; reprogramming; transplantation