Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells  

作　　者：Fengyun Zhang Xiaodan Qian Cheng Qin Yuhui Lin Haiyin Wu Lei Chang Chunxia Luo Dongya Zhu 

机构地区：[1]Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China [2]Institute of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, China [3]Laboratory of Cerebrovascular Disease, Nanjing Medical University, Nanjing 211166, China [4]Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing 211166, China

出　　处：《Neuroscience Bulletin》2016年第3期205-216,共12页神经科学通报（英文版）

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);the Natural Science Foundation of Jiangsu Province,China(BK2011029 and BK20130040);the Collaborative Innovation Center For Cardiovascular Disease Translational Medicine

摘　　要：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.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.

关 键 词：Phosphofructokinase-1 Neural stem cell -Neurogenesis Neuronal differentiation Proliferation Hypoxia 

分 类 号：R338[医药卫生—人体生理学]