期刊
STEM CELL RESEARCH
卷 58, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.scr.2021.102618
关键词
ATM; Neural stem cell; Notch signaling pathway; Quiescence; Aging
资金
- National Natural Science Foundation of China [82171380, 81501189]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [SQ2018ZX090201]
- Application Research Project of Nantong city [JC2019020]
ATM plays a crucial role in maintaining the function of adult neural stem cells by preserving their stemness and preventing cellular senescence primarily through the Notch signaling pathway.
Ataxia telangiectasia mutated (ATM) plays an essential role in DNA damage response and the maintenance of genomic stability. However, the role of ATM in regulating the function of adult neural stem cells (NSCs) remains unclear. Here we report that ATM deficiency led to accumulated DNA damage and decreased DNA damage repair capacity in neural progenitor cells. Moreover, we observed ATM ablation lead to the short-term increase of proliferation of neural progenitor cells, resulting in the depletion of the NSC pool over time, and this loss of NSC quiescence resulted in accelerated cell senescence. We further apply RNA sequencing to unravel that ATM knockout significantly affected Notch signaling pathway, furthermore, notch activation inhibit the abnormal increased proliferation of ATM-/- NSCs. Taken together, these findings indicate that ATM can serve as a key regulator for the normal function of adult NSCs by maintaining their stemness and preventing cellular senescence primarily through Notch signaling pathway.
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