Hematopoietic stem-cell behavior in nonhuman primates
Hematopoietic stem-cell behavior in nonhuman primates
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DOI：
10.1182/blood-2007-02-075382
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发表时间：
2007-09-15
期刊：
影响因子：
20.3
通讯作者：
Abkowitz, Janis L.
中科院分区：
文献类型：
--
作者：
Shepherd, Bryan E.;Kiem, Hans-Peter;Abkowitz, Janis L.
由于直接观察和竞争性再增殖试验不可行，对灵长类动物造血干细胞（HSC）的行为知之甚少。因此，我们使用了2种不同的和独立的实验策略，逆转录病毒介导的基因转移后的转基因表达的跟踪（N = 11狒狒; N = 7恒河猴）和粒细胞的平均端粒长度的定量（N = 132狒狒; N = 14猕猴），连同随机方法，研究HSC在体内的动力学。根据基因标记分析，狒狒HSC的平均复制率为每36周一次，根据端粒缩短分析，每23周一次。从猕猴数据中得出了可比结果。这些速率明显低于先前报道的小鼠（每2.5周一次）和猫（每8.3周一次）中HSC的平均复制速率。由于狒狒和猕猴的寿命为25至45年，比小鼠（近似2年）和猫（12-18年）长得多，我们可以计算出HSC经历相对恒定数量（近似80-200）的终身复制。因此，我们的数据表明，哺乳动物干细胞在体内的自我更新能力是确定的和进化保守的。
Little is known about the behavior of hematopoietic stem cells (HSCs) in primates because direct observations and competitive-repopulation assays are not feasible. Therefore, we used 2 different and independent experimental strategies, the tracking of transgene expression after retroviral-mediated gene transfer (N = 11 baboons; N = 7 rhesus macaques) and quantitation of the average telomere length of granulocytes (N = 132 baboons; N = 14 macaques), together with stochastic methods, to study HSC kinetics in vivo. The average replication rate for baboon HSCs is once per 36 weeks according to gene-marking analyses and once per 23 weeks according to telomere-shortening analyses. Comparable results were derived from the macaque data. These rates are substantially slower than the average replication rates previously reported for HSCs in mice (once per 2.5 weeks) and cats (once per 8.3 weeks). Because baboons and macaques live for 25 to 45 years, much longer than mice (similar to 2 years) and cats (12-18 years), we can compute that HSCs undergo a relatively constant number (similar to 80-200) of lifetime replications. Thus, our data suggest that the self-renewal capacity of mammalian stem cells in vivo is defined and evolutionarily conserved.