title: Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Haiyin
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China.|Institute of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing, 211166, China.|Laboratory of Cerebrovascular Disease, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. dyzhu@njmu.edu.cn.|Institute of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing, 211166, China. dyzhu@njmu.edu.cn.|Laboratory of Cerebrovascular Disease, Nanjing Medical University, Nanjing, 211166, China. dyzhu@njmu.edu.cn.|Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing, 211166, China. dyzhu@njmu.edu.cn.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000235:genetics*; D010732:Phosphofructokinase-1 / Q000235:genetics* / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D051876:Sex-Determining Region Y Protein; C527783:Sox2 protein, mouse; D010732:Phosphofructokinase-1
keywords: Hypoxia; Neural stem cell; Neurogenesis; Neuronal differentiation; Phosphofructokinase-1; Proliferation