Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs.
Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs.
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DOI：
10.1016/j.celrep.2015.11.030
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发表时间：
2015-12-22
期刊：
影响因子：
8.8
通讯作者：
Geiger H
中科院分区：
文献类型：
--
作者：
Moehrle BM;Nattamai K;Brown A;Florian MC;Ryan M;Vogel M;Bliederhaeuser C;Soller K;Prows DR;Abdollahi A;Schleimer D;Walter D;Milsom MD;Stambrook P;Porteus M;Geiger H
衰老的造血干细胞和祖细胞（HSPCs）是否受损DNA损伤修复是有争议的。使用DNA突变指标测定的组合，我们观察到造血系统中DNA突变的数量在衰老时增加了2-3倍。年轻和年老的hsc和HPCs在辐照诱导的DNA损伤修复中没有表现出突变的增加，并且年轻和年老的HSPCs在细胞周期检查点激活和凋亡方面对DNA损伤的反应非常相似。年轻和年老的HSPCs都表现出dna损伤诱导的G1-S检查点的激活受损。锌指核酸酶诱导慢性DNA双链断裂表明HSPCs发生凋亡而不是错误修复。这些数据揭示了一个保护机制，在年轻和老年造血系统对抗积累突变响应DNA损伤。
Whether aged hematopoietic stem and progenitor cells (HSPCs) have impaired DNA damage repair is controversial. Using a combination of DNA mutation indicator assays, we observe a 2-3 fold increase in the number of DNA mutations in the hematopoietic system upon aging. Young and aged HSCs and HPCs do not show an increase in mutation upon irradiation-induced DNA damage repair, and young and aged HSPCs respond very similarly to DNA damage with respect to cell cycle checkpoint activation and apoptosis. Both, young and aged HSPCs show impaired activation of the DNA-damage induced G1-S checkpoint. Induction of chronic DNA double strand breaks by zinc-finger nucleases suggest that HSPCs undergo apoptosis rather than faulty repair. These data reveal a protective mechanism in both the young and aged hematopoietic system against accumulation of mutations in response to DNA damage.