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Transcription factor induction of human oligodendrocyte progenitor fate and differentiation.
Wang, Jing; Pol, Suyog U; Haberman, Alexa K; Wang, Chunming; O'Bara, Melanie A; Sim, Fraser J.
Afiliación
  • Wang J; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
  • Pol SU; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
  • Haberman AK; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
  • Wang C; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
  • O'Bara MA; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214.
  • Sim FJ; Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214 fjsim@buffalo.edu.
Proc Natl Acad Sci U S A ; 111(28): E2885-94, 2014 Jul 15.
Article en En | MEDLINE | ID: mdl-24982138
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Diferenciación Celular / Oligodendroglía / Regulación de la Expresión Génica / Células-Madre Neurales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Diferenciación Celular / Oligodendroglía / Regulación de la Expresión Génica / Células-Madre Neurales Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos