Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

来源 :Neuroscience Bulletin | 被引量 : 0次 | 上传用户:duozhiyu
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Phosphofructokinase-1(PFK-1),a major regulatory glycolytic enzyme,has been implicated in the functions of astrocytes and neurons.Here,we report that PFK-1 negatively regulates neurogenesis from neural stem cells(NSCs)by targeting pro-neural transcriptional factors.Using in vitro assays,we found that PFK-1 knockdown enhanced,and PFK-1 overexpression inhibited the neuronal differentiation of NSCs,which was consistent with the findings from NSCs subjected to 5 h of hypoxia.Meanwhile,the neurogenesis induced by PFK-1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage.Similarly,in vivo knockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus.Finally,we demonstrated that the neurogenesis mediated by PFK-1 was likely achieved by targeting mammalian achaete-scute homologue-1(Mash 1),neuronal differentiation factor(NeuroD),and sex-determining region Y(SRY)-related HMG box 2(Sox2).All together,our results reveal PFK-1 as an important regulator of neurogenesis. Phosphofructokinase-1 (PFK-1), a major regulatory glycolytic enzyme, has been implicated in the functions of astrocytes and neurons. Here, we report that PFK-1 negatively regulates neurogenesis from neural stem cells (NSCs) by targeting pro-neural transcriptional Factors .Using in vitro assays, we found that PFK-1 knockdown enhanced, and PFK-1 overexpression inhibited the neuronal differentiation of NSCs, which was consistent with the findings from NSCs subjected to 5 h of hypoxia.Meanwhile, the neurogenesis induced by PFK -1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage. Similarly, in vivo knockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus. Finaally, we demonstrated that the neurogenesis mediated by PFK-1 was likely targeted by mammalian achaete-scute homologue-1 (Mash 1), neuronal differentiation factor (NeuroD), and sex-determining region Y (SRY) -related HMG box 2 (Sox2) ther, our results reveal PFK-1 as an important regulator of neurogenesis.
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