期刊
BLOOD
卷 110, 期 6, 页码 1806-1813出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-02-075382
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资金
- NHLBI NIH HHS [P50 HL054881, P01 HL053750, R01 HL082933, R01 HL046598, HL082933, HL54881, HL53750] Funding Source: Medline
- NIAID NIH HHS [R01 AI029524, AI29524, R21 AI029524] Funding Source: Medline
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.
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