de Haan G, Nijhof W, Van Zant G
University of Kentucky Medical Center, Division of Hematology/Oncology, Markey Cancer Center, Lexington 40536-0093, USA.
Blood. 1997 Mar 1;89(5):1543-50.
We have quantified the frequency and proliferation of five subsets of primitive hematopoietic cells, using the cobblestone area forming cell (CAFC) assay, in marrow of five strains of mice with lifespans ranging from about 500 to 800 days. Stem cell characteristics were determined in young (6 weeks) and old (12 months) mice. We report striking effects of both intrinsic strain lifespan and individual mouse age on stem cell populations. First, the relative and absolute numbers of the most primitive stem cell subsets was threefold to fourfold higher in old than in young mice. Second, a considerable strain-to-strain variation in the number of primitive cells was observed: when absolute frequencies were calculated, there was a trend for longer lifespan to be correlated with a larger stem cell pool. Third, stem cells from old mice had a far lower cycling activity than cells from young mice. However, this was highly strain dependent: short-lived C3H/He and CBA/J mice showed a stronger reduction in cycling activity during aging than long-lived C57BL/6 mice. Finally, a significant negative correlation was demonstrated in young mice between maximal lifespan and proliferative activity. These data show that aging has a major impact on the frequency and cell-cycle kinetics of primitive hematopoietic cell compartments. In addition, the observation that cycling activity of stem cells is related to the maximal lifespan of the mouse strain may open ways to identify the genetic mechanisms of both strain- and age-dependent variation in the structure of primitive hematopoietic cell compartments.
我们使用鹅卵石区域形成细胞（CAFC）分析方法，对寿命在约500至800天之间的五个品系小鼠的骨髓中五种原始造血细胞亚群的频率和增殖情况进行了量化。在年轻（6周龄）和年老（12月龄）小鼠中测定了干细胞特征。我们报告了内在品系寿命和个体小鼠年龄对干细胞群体的显著影响。首先，最原始的干细胞亚群的相对和绝对数量在年老小鼠中比在年轻小鼠中高出三到四倍。其次，观察到原始细胞数量存在相当大的品系间差异：当计算绝对频率时，有寿命越长与干细胞池越大相关的趋势。第三，年老小鼠的干细胞比年轻小鼠的干细胞具有低得多的循环活性。然而，这高度依赖于品系：短命的C3H/He和CBA/J小鼠在衰老过程中循环活性的降低比长寿的C57BL/6小鼠更强。最后，在年轻小鼠中，最大寿命与增殖活性之间存在显著的负相关。这些数据表明，衰老对原始造血细胞区室的频率和细胞周期动力学有重大影响。此外，干细胞的循环活性与小鼠品系的最大寿命相关这一观察结果可能为确定原始造血细胞区室结构中品系和年龄依赖性变异的遗传机制开辟道路。
