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

Authors :
Chuanming Dong
Xianli Wang
Lixin Sun
Liang Zhu
Danjing Yang
Shane Gao
Wenjun Zhang
Bin Ling
Aibin Liang
Zhengliang Gao
Jun Xu
Source :
Stem Cell Research, Vol 58, Iss , Pp 102618- (2022)
Publication Year :
2022
Publisher :
Elsevier, 2022.

Abstract

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.

Details

Language :
English
ISSN :
18735061
Volume :
58
Issue :
102618-
Database :
Directory of Open Access Journals
Journal :
Stem Cell Research
Publication Type :
Academic Journal
Accession number :
edsdoj.38dfa05996046c58d6ef3062427db26
Document Type :
article
Full Text :
https://doi.org/10.1016/j.scr.2021.102618