Aging of hematopoietic stem cells: DNA damage and mutations?
Aging of hematopoietic stem cells: DNA damage and mutations?
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DOI：
10.1016/j.exphem.2016.06.253
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发表时间：
2016-10
影响因子：
2.6
通讯作者：
Geiger, Hartmut
中科院分区：
文献类型：
--
作者：
Moehrle, Bettina M.;Geiger, Hartmut
造血系统和干细胞生态位中的衰老有助于造血干细胞（hsc）的衰老相关表型，包括白血病和衰老相关的免疫重塑。其中，hsc衰老的DNA损伤理论已经很好地建立起来，基于在彗星试验中检测到大量的γH2AX病灶和更高的尾力矩，这两者最初被认为与衰老hsc的DNA损伤和缺乏DNA修复因子的动物的骨髓衰竭有关。随着年龄的增长，造血系统中DNA突变的增加和性质，衰老的hsc中DNA损伤反应的质量和γ - h2ax焦点的性质等方面的新数据质疑DNA损伤与hsc的DNA损伤反应和衰老之间的直接联系，而认为表观遗传学、剪接因子或细胞三维结构的变化是hsc衰老的主要细胞内在因素。如果hsc老化也是由一个强大的贡献驱动的生态位老化。本文从造血干细胞衰老的新机制出发，对造血干细胞衰老的DNA损伤理论进行了综述。
Aging in the hematopoietic system and the stem cell niche contributes to aging-associated phenotypes of hematopoietic stem cells (HSCs), including leukemia and aging-associated immune remodeling. Among others, the DNA damage theory of aging of HSCs is well established, based on the detection of a significantly higher amount of γH2AX foci and a higher tail moment in the comet assay, both initially thought to be associated with DNA damage in aged HSCs compared to young cells, and bone marrow failure in animals devoid of DNA repair factors. Novel data on the increase and the nature of DNA mutations in the hematopoietic system upon aging, the quality of the DNA damage response in aged HSCs and the nature of γH2AX foci question a direct link between DNA damage and the DNA damage response and aging of HSCs, and rather favor changes in epigenetics, splicing-factors or 3D architecture of the cell as major cell intrinsic factors of HSCs aging. Aging if HSCs is also driven by a strong contribution of aging of the niche. This review discusses the DNA damage theory of HSCs aging in the light of these novel mechanisms of aging of HSCs.
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DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
10.5
作者：
Bender, CF;Sikes, ML;Petrini, JHJ
通讯作者：
Petrini, JHJ
影响因子：
23.9
作者：
Florian, Maria Carolina;Doerr, Karin;Niebel, Anja;Daria, Deidre;Schrezenmeier, Hubert;Rojewski, Markus;Filippi, Marie-Dominique;Hasenberg, Anja;Gunzer, Matthias;Scharffetter-Kochanek, Karin;Zheng, Yi;Geiger, Hartmut
通讯作者：
Geiger, Hartmut
影响因子：
64.5
作者：
Barlow, C;Hirotsune, S;WynshawBoris, A
通讯作者：
WynshawBoris, A
影响因子：
64.8
作者：
Janzen, Viktor;Forkert, Randolf;Scadden, David T.
通讯作者：
Scadden, David T.