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

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

Research output: Contribution to journalArticle

522 Citations (Scopus)

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 (US)
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
StatePublished - Nov 23 2004

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Histone Deacetylases
Valproic Acid
Stem Cells
Neuroglia
Basic Helix-Loop-Helix Transcription Factors
Histone Deacetylase Inhibitors
Oligodendroglia
Astrocytes
Chromatin
Transcription Factors
Gene Expression
Neurons
Genes

Keywords

  • Cell fate specification
  • Chromatin
  • Neural stem cell
  • Valproic acid

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. / Hsieh, Jenny; Nakashima, Kinichi; Kuwabara, Tomoko; Mejia, Eunice; Gage, Fred H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 47, 23.11.2004, p. 16659-16664.

Research output: Contribution to journalArticle

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