DNA damage: a sensible mediator of the differentiation decision in hematopoietic stem cells and in leukemia.
DNA damage: a sensible mediator of the differentiation decision in hematopoietic stem cells and in leukemia.
复制标题
DNA损伤：造血干细胞和白血病中分化决策的明智介质。
DOI：
10.3390/ijms16036183
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发表时间：
2015-03-17
影响因子：
5.6
通讯作者：
Ito K
中科院分区：
文献类型：
--
作者：
Weiss CN;Ito K
在成人中，功能多样的成熟血细胞的来源是造血干细胞，这是一种罕见的静止细胞群，位于骨髓龛中。与其他组织中的干细胞一样，造血干细胞通过其自我更新的能力来定义，以便在生物体的一生中维持干细胞群体，并且分化，以便产生造血系统的多个谱系。近年来，越来越多的证据表明活性氧的积累和DNA损伤在造血干细胞退出静止期和分化的决定中起作用。在这篇综述中，我们将研究最近的工作支持的想法，检测细胞应激，如氧化和遗传损伤，是造血干细胞的细胞命运决定的重要介质。我们将探索这种系统在避免恶性肿瘤的发展和进展以及避免组织衰竭和失败方面的益处。此外，我们将讨论新的工作，检查老化造血干细胞中DNA损伤和复制应激的积累，并使我们重新思考骨髓生态位中基因保护的想法。
In the adult, the source of functionally diverse, mature blood cells are hematopoietic stem cells, a rare population of quiescent cells that reside in the bone marrow niche. Like stem cells in other tissues, hematopoietic stem cells are defined by their ability to self-renew, in order to maintain the stem cell population for the lifetime of the organism, and to differentiate, in order to give rise to the multiple lineages of the hematopoietic system. In recent years, increasing evidence has suggested a role for the accumulation of reactive oxygen species and DNA damage in the decision for hematopoietic stem cells to exit quiescence and to differentiate. In this review, we will examine recent work supporting the idea that detection of cell stressors, such as oxidative and genetic damage, is an important mediator of cell fate decisions in hematopoietic stem cells. We will explore the benefits of such a system in avoiding the development and progression of malignancies, and in avoiding tissue exhaustion and failure. Additionally, we will discuss new work that examines the accumulation of DNA damage and replication stress in aging hematopoietic stem cells and causes us to rethink ideas of genoprotection in the bone marrow niche.
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