Glutaminase 1 is essential for the differentiation, proliferation, and survival of human neural progenitor cells

Yi Wang, Yunlong Huang, Lixia Zhao, Yuju Li, Jialin Zheng

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Previous studies have revealed that mice lacking glutaminase 1 (GLS1), the dominant isoform in the brain and kidney, died shortly after birth due to disrupted glutamatergic transmission, suggesting the critical role of GLS1 in the physiological functions of synaptic network. However, whether GLS1 regulates neurogenesis, a process by which neurons are generated from neural progenitor cells (NPCs), is unknown. Using a human NPC model, we found that both GLS1 isotypes, kidney-type glutaminase and glutaminase C, were upregulated during neuronal differentiation, which were correlated with the expression of neuronal marker microtubule-associated protein 2 (MAP-2). To study the functional impact of GLS1 on neurogenesis, we used small interference RNA targeting GLS1 and determined the expressions of neuronal genes by western blot, real-time polymerase chain reaction, and immunocytochemistry. siRNA silencing of GLS1 significantly reduced the expression of MAP-2, indicating that GLS1 is essential for neurogenesis. To unravel the specific process(es) of neurogenesis being affected, we further studied the proliferation and survival of NPCs in vitro. siRNA silencing of GLS1 significantly reduced the Ki67+ and increased the TUNEL+ cells, suggesting critical roles of GLS1 for the proliferation and survival of NPCs. Together, these data suggest that GLS1 is critical for proper functions of NPCs, including neuronal differentiation, proliferation, and survival.

Original languageEnglish (US)
Pages (from-to)2782-2790
Number of pages9
JournalStem Cells and Development
Volume23
Issue number22
DOIs
StatePublished - Nov 15 2014

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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