Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells.
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.
Hsieh
Jenny
J
Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA.
Nakashima
Kinichi
K
Kuwabara
Tomoko
T
Mejia
Eunice
E
Gage
Fred H
FH
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology
D051792:Basic Helix-Loop-Helix Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D009419:Nerve Tissue Proteins; D014635:Valproic Acid; C093564:Neurogenic differentiation factor 1