Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells
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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.
KeywordsPhosphofructokinase-1 Neural stem cell Neurogenesis Neuronal differentiation Proliferation Hypoxia
This work was supported by grants from the National Natural Science Foundation of China (91232304, 31530091, and 81571188), the National Basic Research Development Program (973 Program) of China (2011CB504404), the Natural Science Foundation of Jiangsu Province, China (BK2011029 and BK20130040), and the Collaborative Innovation Center For Cardiovascular Disease Translational Medicine.
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