Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation
Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation
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DOI：
10.1182/blood-2002-07-2334
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发表时间：
2003-07-15
期刊：
影响因子：
20.3
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Allsopp, RC;Morin, GB;Weissman, IL
端粒缩短最终限制了培养的人体细胞的复制寿命。端粒在造血细胞中体内复制衰老期间也缩短了来自人类和小鼠的早期造血祖细胞和造血干细胞（HSC），尽管这些细胞中的端粒酶水平很容易检测到。为了评估端粒酶与体内HSC的长期复制能力的相关性，我们从野生型和缺陷型小鼠中串行移植HSC，直到在此过程中疲惫并监测HSC中的端粒长度。缺乏端粒酶的HSC只能连续移植2发，而野生型HSC至少可以连续移植4发。此外，在端粒酶缺陷型HSC的连续移植过程中，端粒缩短的速率增加了约2倍。这些发现表明，HSC中端粒酶的一个作用是部分应对HSC分裂期间端粒缩短的速率，从而防止端粒功能的过早损失并提供增加的复制能力。 （c）2003年美国血液学学会。
Telomere shortening ultimately limits the replicative life span of cultured human somatic cells. Telomeres also shorten during replicative aging in vivo in hematopoietic cells, including early hematopoietic progenitors and hematopoietic stem cells (HSCs), from humans and mice, despite readily detectable levels of telomerase in these cells. To assess the relevance of telomerase to the long-term replicative capacity of HSCs in vivo, we serially transplanted HSCs from wild-type and telomerase-deficient mice until exhaustion and monitored telomere length in HSCs during this process. Telomerase-deficient HSCs could be serially transplanted for only 2 rounds, whereas wild-type HSCs could be serially transplanted for at least 4 rounds. Furthermore, the rate of telomere shortening was increased approximately 2-fold during serial transplantation of telomerase-deficient HSCs. These findings suggest that one role for telomerase in the HSC is to partially counter the rate of telomere shortening during division of HSCs, thereby preventing premature loss of telomere function and providing added replicative capacity. (C) 2003 by The American Society of Hematology.