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

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.

Keywords

Phosphofructokinase-1, Neural stem cell, Neurogenesis, Neuronal differentiation, Proliferation, Hypoxia

[SpringerLink]