Weiss Cary N, Ito Keisuke
Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Departments of Cell Biology/Stem Cell Institute and Medicine, Albert Einstein Cancer Center and Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Int J Mol Sci. 2015 Mar 17;16(3):6183-201. doi: 10.3390/ijms16036183.
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.
在成年人中，功能多样的成熟血细胞的来源是造血干细胞，这是一类罕见的静止细胞群体，存在于骨髓微环境中。与其他组织中的干细胞一样，造血干细胞的定义在于其自我更新能力，以便在生物体的整个生命周期中维持干细胞群体，以及分化能力，从而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状态并进行分化的过程中发挥了作用。在这篇综述中，我们将审视最近的研究工作，这些工作支持这样一种观点，即细胞应激源（如氧化和遗传损伤）的检测是造血干细胞命运决定的重要介导因素。我们将探讨这样一个系统在避免恶性肿瘤的发生和发展以及避免组织耗竭和功能衰竭方面的益处。此外，我们将讨论新的研究工作，这些工作研究了衰老造血干细胞中DNA损伤和复制应激的积累，并促使我们重新思考骨髓微环境中的基因保护观念。
