Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
J Hematol Oncol. 2020 Apr 6;13(1):31. doi: 10.1186/s13045-020-00864-8.
Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.
造血干细胞（HSC）衰老伴随着自我更新能力下降、归巢受损、向髓系分化偏倚以及造血重建功能的其他缺陷，是干细胞研究的热点。尽管小鼠和人类的 HSC 数量随年龄增长而增加，但增加量无法弥补衰老 HSC 的缺陷。许多研究从不同角度阐明了 HSC 衰老的潜在机制；然而，详细的分子机制仍不清楚，阻碍了对衰老 HSC 年轻化的进一步探索。为了确定衰老 HSC 缺陷是如何发生的，我们概述了年轻和衰老 HSC 的特征、信号通路和表观遗传学以及 HSC 所在的骨髓龛之间的差异。值得注意的是，我们总结了最近在单细胞水平上解析 HSC 衰老的研究。此外，我们还综述了恢复衰老 HSC 功能的有前途的策略。鉴于许多血液系统恶性肿瘤的发病率与年龄密切相关，我们的 HSC 衰老综述阐明了功能变化与分子机制之间的联系，可能具有重要的临床意义。
