Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells

Jenny Hsieh, Kinichi Nakashima, Tomoko Kuwabara, Eunice Mejia, Fred H. Gage

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Abstract

It has become apparent that chromatin modification plays a critical role in the regulation of cell-type-specific gene expression. Here, we show that an inhibitor of histone deacetylase, valproic acid (VPA), induced neuronal differentiation of adult hippocampal neural progenitors. In addition, VPA inhibited astrocyte and oligodendrocyte differentiation, even in conditions that favored lineage-specific differentiation. Among the VPA-up-regulated, neuron-specific genes, a neurogenic basic helix-loop-helix transcription factor, NeuroD, was identified. Overexpression of NeuroD resulted in the induction and suppression of neuronal and glial differentiation, respectively. These results suggest that VPA promotes neuronal fate and inhibits glial fate simultaneously through the induction of neurogenic transcription factors including NeuroD.

Original languageEnglish
Pages (from-to)16659-16664
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number47
DOIs
Publication statusPublished - Nov 23 2004
Externally publishedYes

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