PI3K/AKT/mTOR Signaling Mediates Valproic Acid-Induced Neuronal Differentiation of Neural Stem Cells through Epigenetic Modifications

• DOI: 10.1016/j.stemcr.2017.04.006
• Publication Date: 2017-05-09T18:58:56Z
• Authors: Xi Zhang; Xiaosong He; Qingqing Li; Xuejian Kong; Zhenri Ou; Le Zhang; Zhuo Gong; Dahong Long; Jianhua Li; Meng Zhang; Weidong Ji; Wenjuan Zhang; Liping Xu; Aiguo Xuan
• Keywords: DNA demethylation; Demethylation

Although valproic acid (VPA), has been shown to induce neuronal differentiation of neural stem cells (NSCs), the underlying mechanisms remain poorly understood. Here we investigated if and how mammalian target rapamycin (mTOR) signaling is involved in VPA-induced NSCs. Our data demonstrated that mTOR activation not only promoted but also was necessary for NSCs induced by VPA. We further found inhibition blocked demethylation neuron-specific gene neurogenin 1 (Ngn1) regulatory element cells. These are correlated with significant alterations passive DNA active pathway Ngn1 promoter, suppression lysine-specific histone methylation acetylation promoter region Ngn1. findings highlight a potentially important role signaling, working together demethylation, influence fate via regulating expression