Histone deacetylase activity is required for human oligodendrocyte progenitor differentiation.
Glia
; 60(12): 1944-53, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22927334
The molecular mechanisms controlling human oligodendrocyte development are poorly characterized. Microarray analysis of human oligodendrocyte progenitor cells (OPCs) and immature oligodendrocytes revealed that specific-class I histone deacetylase (HDAC) target genes were actively repressed during oligodendrocyte commitment. Although epigenetic regulation of oligodendrocyte differentiation has been established in rodent development, the role of HDACs in human OPCs remains undefined. We used HDAC inhibitors (HDACi) trichostatin A (TSA) and sodium butyrate to determine the importance of HDAC activity in human primary OPC differentiation. Treatment with either drug resulted in significant dose-dependent inhibition of O4(+) oligodendrocyte cell differentiation, reduction of oligodendrocyte morphological maturation, and downregulation of myelin basic protein mRNA. High dose TSA treatment was also associated with reduction in OPC proliferation. HDACi treatment prevented downregulation of SOX2, ID4, and TCF7L2 mRNAs but did not regulate HES5, suggesting that targets of HDAC repression may differ between species. These results predict that HDACi treatment would impair proliferation and differentiation by parenchymal oligodendrocyte progenitors, and thereby degrade their potential for endogenous repair in human demyelinating disease. © 2012 Wiley Periodicals, Inc.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
/
Oligodendroglía
/
Células Madre Embrionarias
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Inhibidores de Histona Desacetilasas
/
Histona Desacetilasas
Límite:
Humans
Idioma:
En
Revista:
Glia
Asunto de la revista:
NEUROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos