Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element

被引:44
作者
Geiger, H [1 ]
Rennebeck, G
Van Zant, G
机构
[1] Childrens Hosp, Med Ctr, Dept Pediat, Div Expt Hematol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA
[3] Univ Kentucky, Lucille P Markey Canc Ctr, Dept Internal Med, Lexington, KY 40536 USA
[4] Univ Kentucky, Lucille P Markey Canc Ctr, Dept Physiol, Lexington, KY 40536 USA
关键词
congenic; DNA damage;
D O I
10.1073/pnas.0408654102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Until recently, stem cells were thought to be endowed with unlimited self-renewal capacity and, thus, assumed exempt from aging. But accumulating evidence over the past decade compellingly argues that a measurable and progressive replicative impairment in the hematopoietic, intestinal, and muscle stem cell activity exists from adulthood to old age, resulting in a decline in stem cell function and rendering stem cell aging as the possible link between cellular aging and organismal aging. By using a previously uncharacterized congenic animal model to study genetic regulation of hematopoietic stem cell aging, we have demonstrated definitively that a locus on murine chromosome 2 regulates hematopoietic stem cell aging. In addition to demonstrating that hematopoietic stem cell aging is regulated by a distinct genetic element, experimental evidence links the response of hematopoietic stem cells to DNA double-strand breaks to cellular aging, suggesting DNA integrity influences stem cell aging.
引用
收藏
页码:5102 / 5107
页数:6
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