衰老中的克隆造血。

IF 2.3 Q4 CELL & TISSUE ENGINEERING Current Stem Cell Reports Pub Date : 2018-09-01 Epub Date: 2018-07-19 DOI:10.1007/s40778-018-0133-9
Soo J Park, Rafael Bejar
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引用次数: 16

摘要

综述目的:克隆性不确定潜能造血(CHIP)是一种常见的、与年龄相关的疾病,其特征是获得体细胞突变。这篇简明的综述探讨了我们目前对影响克隆与衰老发展的机制及其潜在的恶性和非恶性临床意义的理解。最近的发现:造血系统的老化导致表型变化,有利于克隆优势。细胞外部因素提供额外的选择压力,进一步塑造克隆结构。即便如此,具有候选驱动突变的小型克隆似乎随着年龄的增长而普遍存在,而且在缺乏强大的选择压力的情况下,它们大多是良性的。良性克隆扩增可以补偿随着年龄增长而丧失的HSC再生能力。CHIP是一种衰老标志物,反映了HSC衰老与细胞外源性因素之间的生物学相互作用。CHIP的临床意义是高度可变的,取决于临床情况。区分调节克隆行为的因果关系和混杂因素对于确定CHIP在衰老中的机制作用并可能减轻其临床后果至关重要。
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Clonal Hematopoiesis in Aging.

Purpose of review: Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition characterized by the acquisition of somatic mutations. This concise review explores our current understanding of the mechanisms that influence the development of clonality with aging and its potential malignant and non-malignant clinical implications.

Recent findings: Aging of the hematopoietic system results in phenotypic changes that favor clonal dominance. Cell-extrinsic factors provide additional selective pressures that further shape clonal architecture. Even so, small clones with candidate driver mutations appear to be ubiquitous with age and largely benign in the absence of strong selective pressures. Benign clonal expansion may compensate for the loss of regenerative HSC capacity as we age.

Summary: CHIP is a marker of aging that reflects the biologic interplay between HSC aging and cell-extrinsic factors. The clinical significance of CHIP is highly variable and dependent on clinical context. Distinguishing the causal relationships and confounding factors that regulate clonal behavior will be essential to define the mechanistic role of CHIP in aging and potentially mitigate its clinical consequences.

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来源期刊
Current Stem Cell Reports
Current Stem Cell Reports Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.30
自引率
0.00%
发文量
19
期刊介绍: The goal of this journal is to publish cutting-edge reviews on subjects pertinent to all aspects of stem cell research, therapy, ethics, commercialization, and policy. We aim to provide incisive, insightful, and balanced contributions from leading experts in each relevant domain that will be of immediate interest to a wide readership of clinicians, basic scientists, and translational investigators. We accomplish this aim by appointing major authorities to serve as Section Editors in key subject areas across the discipline. Section Editors select topics to be reviewed by leading experts who emphasize recent developments and highlight important papers published over the past year on their topics, in a crisp and readable format. We also provide commentaries from well-known figures in the field, and an Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.
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