ATM modulates subventricular zone neural stem cell maintenance and senescence through Notch signaling pathway

Autor: Chuanming Dong, Xianli Wang, Lixin Sun, Liang Zhu, Danjing Yang, Shane Gao, Wenjun Zhang, Bin Ling, Aibin Liang, Zhengliang Gao, Jun Xu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Stem Cell Research, Vol 58, Iss , Pp 102618- (2022)
Druh dokumentu: article
ISSN: 1873-5061
DOI: 10.1016/j.scr.2021.102618
Popis: 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.
Databáze: Directory of Open Access Journals