Shepherd Bryan E, Kiem Hans-Peter, Lansdorp Peter M, Dunbar Cynthia E, Aubert Geraldine, LaRochelle Andre, Seggewiss Ruth, Guttorp Peter, Abkowitz Janis L
Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
Blood. 2007 Sep 15;110(6):1806-13. doi: 10.1182/blood-2007-02-075382. Epub 2007 May 25.
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 ( approximately 2 years) and cats (12-18 years), we can compute that HSCs undergo a relatively constant number ( approximately 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.
由于直接观察和竞争性再增殖试验不可行，关于灵长类动物造血干细胞（HSC）的行为了解甚少。因此，我们使用了两种不同且独立的实验策略，即逆转录病毒介导的基因转移后追踪转基因表达（11只狒狒；7只恒河猴）和定量粒细胞的平均端粒长度（132只狒狒；14只猕猴），并结合随机方法，来研究体内HSC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，根据端粒缩短分析为每23周一次。猕猴数据得出了类似结果。这些速率明显慢于先前报道的小鼠（每2.5周一次）和猫（每8.3周一次）的HSC平均复制率。由于狒狒和猕猴的寿命为25至45年，远长于小鼠（约2年）和猫（12 - 18年），我们可以计算出HSC在一生中经历相对恒定数量（约80 - 200次）的复制。因此，我们的数据表明，体内哺乳动物干细胞的自我更新能力是确定的且在进化上是保守的。
