EVIDENCE FOR A MITOTIC CLOCK IN HUMAN HEMATOPOIETIC STEM-CELLS - LOSS OF TELOMERIC DNA WITH AGE
EVIDENCE FOR A MITOTIC CLOCK IN HUMAN HEMATOPOIETIC STEM-CELLS - LOSS OF TELOMERIC DNA WITH AGE
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DOI：
10.1073/pnas.91.21.9857
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
LANSDORP, PM
中科院分区：
文献类型：
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作者：
VAZIRI, H;DRAGOWSKA, W;LANSDORP, PM
在整个生命过程中维持造血的干细胞的增殖寿命尚不清楚。有人提出，随着每次体细胞分裂，端粒DNA从人类染色体末端的顺序丢失最终达到触发细胞衰老的临界点。我们现在发现，从成人骨髓中纯化的具有CD34（+）CD38（lo）表型的候选人干细胞比来自胎儿肝脏或脐带血的细胞具有更短的端粒。我们还发现，在纯化的前体细胞的补充精氨酸的培养物中产生的细胞显示与端粒DNA的增殖相关的损失。这些研究结果强烈表明，大多数（如果不是全部）造血干细胞的增殖潜力是有限的，并随着年龄的增长而降低，这一概念对正常和异常造血模型以及基因治疗具有广泛的影响。
The proliferative life-span of the stem cells that sustain hematopoiesis throughout life is not known. It has been proposed that the sequential loss of telomeric DNA from the ends of human chromosomes with each somatic cell division eventually reaches a critical point that triggers cellular senescence. We now show that candidate human stem cells with a CD34(+)CD38(lo) phenotype that were purified from adult bone marrow have shorter telomeres than cells from fetal liver or umbilical cord blood. We also found that cells produced in cytokine-supplemented cultures of purified precursor cells show a proliferation-associated loss of telomeric DNA. These findings strongly suggest that the proliferative potential of most, if not all, hematopoietic stem cells is limited and decreases with age, a concept that has widespread implications for models of normal and abnormal hematopoiesis as well as gene therapy.