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（N...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.展开更多
基金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)+1 种基金the Natural Science Foundation of Jiangsu Province,China(BK2011029 and BK20130040)the Collaborative Innovation Center For Cardiovascular Disease Translational Medicine
文摘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.
