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

被引:572
作者
Hsieh, J
Nakashima, K [1 ]
Kuwabara, T
Mejia, E
Gage, FH
机构
[1] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
[2] Nara Inst Sci & Technol, Lab Mol Neurosci, Grad Sch Biol Sci, Ikoma 6300101, Japan
关键词
cell fate specification; chromatin; neural stem cell; valproic acid;
D O I
10.1073/pnas.0407643101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:16659 / 16664
页数:6
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