Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells
Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells
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DOI：
10.1073/pnas.0407643101
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发表时间：
2004-11-23
影响因子：
11.1
通讯作者：
Gage, FH
中科院分区：
文献类型：
--
作者：
Hsieh, J;Nakashima, K;Gage, FH
染色质修饰在细胞类型特异性基因表达的调控中起着至关重要的作用。在这里，我们展示了组蛋白脱乙酰酶的抑制剂，丙戊酸(VPA)，诱导成年海马神经祖细胞分化。此外，VPA抑制星形胶质细胞和少突胶质细胞的分化，即使在有利于谱系特异性分化的条件下也是如此。在VPA上调的神经元特异性基因中，发现了一种神经源性的碱性螺旋-环-螺旋转录因子--NeuD。神经D的过度表达分别导致神经元和神经胶质细胞分化的诱导和抑制。这些结果表明，VPA通过诱导包括NeuD在内的神经源性转录因子，促进神经元的命运，同时抑制神经胶质的命运。
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.