The replication rate of human hematopoietic stem cells in vivo
The replication rate of human hematopoietic stem cells in vivo
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DOI：
10.1182/blood-2010-08-303537
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发表时间：
2011-04-28
期刊：
影响因子：
20.3
通讯作者：
Abkowitz, Janis L.
中科院分区：
文献类型：
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作者：
Catlin, Sandra N.;Busque, Lambert;Abkowitz, Janis L.
造血干细胞(HSCs)复制(自我更新)以产生两个子代细胞，具有与其亲代相同的能力，并具有分化的能力，因此可以维持和恢复血细胞的产生。用分裂敏感标记的细胞标记和竞争性移植研究已经被用来估计小鼠HSCs在体内的复制率。然而，这些方法在人类身上是不可行的，需要进行替代分析。在这份报告中，我们分析了女性血细胞中母系/父系X染色体表型随年龄变化的比率，并推断人类造血干细胞平均每40周(范围为25-50周)复制一次。然后，我们用两种独立的方法证实了这一估计，并使用该估计来模拟人类的造血，并表明模拟准确地再现了骨髓移植的数据。我们的模拟也提供了证据，从出生到青春期，人类的HSCs数量增加，然后进入高原，人类HSCs静止的比例与小鼠显著不同。此外，他们提出，人类骨髓衰竭，如脐带血移植后发生的骨髓衰竭和再生障碍性贫血，是由于早期祖细胞数量不足造成的，而不是缺乏造血干细胞。(血。2011；117(17)：4460-4466)
Hematopoietic stem cells (HSCs) replicate (self-renew) to create 2 daughter cells with capabilities equivalent to their parent, as well as differentiate, and thus can both maintain and restore blood cell production. Cell labeling with division-sensitive markers and competitive transplantation studies have been used to estimate the replication rate of murine HSCs in vivo. However, these methods are not feasible in humans and surrogate assays are required. In this report, we analyze the changing ratio with age of maternal/paternal X-chromosome phenotypes in blood cells from females and infer that human HSCs replicate on average once every 40 weeks (range, 25-50 weeks). We then confirm this estimate with 2 independent approaches, use the estimate to simulate human hematopoiesis, and show that the simulations accurately reproduce marrow transplantation data. Our simulations also provide evidence that the number of human HSCs increases from birth until adolescence and then plateaus, and that the ratio of contributing to quiescent HSCs in humans significantly differs from mouse. In addition, they suggest that human marrow failure, such as the marrow failure that occurs after umbilical cord blood transplantation and with aplastic anemia, results from insufficient numbers of early progenitor cells, and not the absence of HSCs. (Blood. 2011; 117(17):4460-4466)