Awakening dormant haematopoietic stem cells
Awakening dormant haematopoietic stem cells
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DOI：
10.1038/nri2726
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发表时间：
2010-03-01
影响因子：
100.3
通讯作者：
Wilson, Anne
中科院分区：
文献类型：
--
作者：
Trumpp, Andreas;Essers, Marieke;Wilson, Anne
小鼠骨髓中的造血干细胞（hsc）作为单个细胞位于特定的壁龛中。在稳态过程中，来自这种环境的信号使一些造血干细胞处于休眠状态，从而保持长期的自我更新潜力，而另一些造血干细胞则主动自我更新以维持造血功能。作为对造血压力的反应，休眠的造血干细胞被激活并迅速补充造血系统。有趣的是，有三种因子——粒细胞集落刺激因子、干扰素- α和三氧化二砷——已被证明能有效地激活休眠干细胞，从而打破它们对抗增殖化疗药物的抵抗力。因此，我们提出两步策略可以通过用休眠激活剂启动肿瘤，然后进行化疗或靶向治疗来靶向耐药白血病干细胞。
Haematopoietic stem cells (HSCs) in mouse bone marrow are located in specialized niches as single cells. During homeostasis, signals from this environment keep some HSCs dormant, which preserves long-term self-renewal potential, while other HSCs actively self renew to maintain haematopoiesis. In response to haematopoietic stress, dormant HSCs become activated and rapidly replenish the haematopoietic system. Interestingly, three factors-granulocyte colony-stimulating factor, interferon-alpha and arsenic trioxide-have been shown to efficiently activate dormant stem cells and thereby could break their resistance to anti-proliferative chemotherapeutics. Thus, we propose that two-step strategies could target resistant leukaemic stem cells by priming tumours with activators of dormancy followed by chemotherapy or targeted therapies.