Acta Anatomica Sinica ›› 2022, Vol. 53 ›› Issue (5): 545-550.doi: 10.16098/j.issn.0529-1356.2022.05.001

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Role of ataxia-telangiectasia mutated gene in maintaining quiescence of neural stem cell from subgranular zone of mouse hippocampus

DONG  Chuan-ming*  HE  Wen-hua#br#   

  1. Department of Human Anatomy,Medical College of Nantong University, Jiangsu Key Laboratory of Nerve Regeneration, Collaborative Innovation Center of Nerve Regeneration, Jiangsu Nantong 226001,China
  • Received:2022-04-08 Revised:2022-05-30 Online:2022-10-06 Published:2022-10-06
  • Contact: DONG Chuan-ming E-mail:yiyimarket@163.com

Abstract:

Objective  To investigate the role of ataxia-telangiectasia mutated gene (ATM) in maintaining quiescence of neural stem cells (NSCs) from subgranular zone (SGZ) of hippocampal dentate gyrus in mice.    Methods  We constructed 1-month-old and 4-month-old mice ATM knockout mice, with 12 mice in each group. The NSCs in SGZ of ATM knockout mice were isolated, cultured and identified in vitro. The proliferation ability of NSCs in SGZ of 1-month-old ATM+/+ and ATM-/- mice were compared by Nestin/ki67 staining; BrdU staining was used to compare the proliferation ability of cells between the two groups in 1-month-old and 4-month-old mice in SGZ, and glial fibrillary acidic protein (GFAP)/sex determining region Y-box 2 (SOX2) staining was used to detect the difference in the proportion of quiescent NSCs between the two groups in SGZ of 4-month-old mice.    Results   Abnormal increased proliferation of NSCs in 1 month-old ATM-/-mice detected by Nestin/ki67 staining in vitro and BrdU staining in vivo(P<0.05). At the age of 4 months, BrdU staining in vivo showed that the proliferation of NSCs in the SGZ of ATM-/- mice decreased significantly(P<0.01), and GFAP/SOX2 staining showed that the proportion of quiescent NSCs in SGZ of ATM-/- mice decreased significantly(P<0.01).  Conclusion  ATM deficiency reduces NSCs quiescence, thus leading to increased activation, proliferation and eventual exhaustion of NSCs, suggesting that ATM can maintain the neural stem cell quiescence. 

Key words: Ataxia-telangiectasia mutated gene, Neural stem cell, Quiescence, Immunofluorescence, Mouse

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