Chen Jichun
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1202, USA.
Int J Hematol. 2005 Oct;82(3):190-5. doi: 10.1532/IJH97.05094.
Functional failure in hematopoietic stem cells (HSCs) may bring fatal consequences because HSCs are the ultimate source of mature blood cells, which need continuous replenishment. One potential cause of HSC dysfunction is senescence, in which HSCs and progenitor cells enter a state of proliferative arrest. HSC senescence is genetically regulated and one particular regulator is the telomerase gene. Mutations in the telomerase gene complex have been found in patients with bone marrow failure syndromes. During a normal lifetime, HSC clones function over the long term and may not show any functional loss under normal circumstances. However, pathologic environments may limit HSC proliferation, accelerate HSC turnover, and shorten the functional life of HSCs, leading to HSC clonal exhaustion and senescence.
造血干细胞（HSCs）功能衰竭可能会带来致命后果，因为造血干细胞是成熟血细胞的最终来源，而成熟血细胞需要持续补充。造血干细胞功能障碍的一个潜在原因是衰老，在此过程中造血干细胞和祖细胞进入增殖停滞状态。造血干细胞衰老受基因调控，其中一个特定的调节因子是端粒酶基因。在骨髓衰竭综合征患者中已发现端粒酶基因复合体的突变。在正常寿命期间，造血干细胞克隆长期发挥功能，在正常情况下可能不会表现出任何功能丧失。然而，病理环境可能会限制造血干细胞的增殖，加速造血干细胞的更新，并缩短造血干细胞的功能寿命，导致造血干细胞克隆性耗竭和衰老。
