Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones
Studies of c-Mpl function distinguish the replication of hematopoietic stem cells from the expansion of differentiating clones
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DOI：
10.1182/blood-2006-08-044503
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发表时间：
2007-06-15
期刊：
影响因子：
20.3
通讯作者：
Chen, Jing
中科院分区：
文献类型：
--
作者：
Abkowitz, Janis L.;Chen, Jing
造血干细胞 (HSC) 具有三个特性：静止和长期存活的能力、自我更新的能力以及产生分化和成熟血细胞的多谱系克隆的能力。尽管可能有不同的信号调节这些事件，但这很难在分子水平上剖析，因为 HSC 分裂、它们的命运决定以及最早的分化事件无法直接可视化。我们对 c-Mpl（细胞因子血小板生成素的细胞受体）的研究表明，c-Mpl 并不像之前所争论的那样控制 HSC 数量，而是促进分化克隆的早期扩增。这些实验提供了一种区分 HSC 与体内最早祖细胞的作用的策略，并证明 HSC 远端水平的选择性生长优势可以对多系造血产生深远的影响。
Three properties define hematopoietic stem cells (HSCs): their capacity for quiescence and long survival, their ability to self-renew, and their ability to give rise to a multilineage clone of differentiating and maturing blood cells. Although it is likely that different signals regulate these events, this has been difficult to dissect on a molecular level, since HSC division, their fate decisions, and the earliest differentiation events cannot be directly visualized. Our studies of c-Mpl, the cellular receptor for the cytokine thrombopoletin, suggest that c-Mpl does not control HSC numbers, as had been previously argued, but rather facilitates the early expansion of differentiating clones. These experiments provide a strategy to distinguish the actions of HSCs from earliest progenitor cells in vivo and demonstrate that a selective growth advantage at a level distal to HSC can result in a profound effect on multilineage hematopoiesis.