Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair
Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair
复制标题
DOI：
10.1016/j.cell.2008.10.048
复制
发表时间：
2008-12-12
期刊：
影响因子：
64.5
通讯作者：
Trumpp, Andreas
中科院分区：
文献类型：
--
作者：
Wilson, Anne;Laurenti, Elisa;Trumpp, Andreas
骨髓造血干细胞（HSC）是维持所有血细胞终身生产的关键。虽然HSC分裂不频繁，但人们认为整个HSC库每隔几周就会翻转一次，这表明HSC有规律地进入和退出细胞周期。在此，我们将联合收割机流式细胞术与标记保留试验（BrdU和组蛋白H2 B-GFP）相结合，以鉴定lin（-）Sca 1（+）cKit（+）CD 150（+）CD 48（-）CD 34（-）群体中的休眠小鼠HSC（d-HSC）群体。计算模型表明，d-HSC大约每145天分裂一次，或每个生命周期分裂5次。d-HSC具有绝大多数的多谱系长期自我更新活性。虽然它们在体内平衡期间形成最有效的HSC的沉默储库，但它们响应于骨髓损伤或G-CSF刺激而被有效地激活以自我更新。在重建稳态后，活化的HSC恢复休眠，表明HSC不是随机进入细胞周期，而是在造血应激条件下可逆地从休眠转换为自我更新。
Bone marrow hematopoietic stem cells (HSCs) are crucial to maintain lifelong production of all blood cells. Although HSCs divide infrequently, it is thought that the entire HSC pool turns over every few weeks, suggesting that HSCs regularly enter and exit cell cycle. Here, we combine flow cytometry with label-retaining assays (BrdU and histone H2B-GFP) to identify a population of dormant mouse HSCs (d-HSCs) within the lin(-)Sca1(+)cKit(+)CD150(+)CD48(-)CD34(-) population. Computational modeling suggests that d-HSCs divide about every 145 days, or five times per lifetime. d-HSCs harbor the vast majority of multilineage long-term self-renewal activity. While they form a silent reservoir of the most potent HSCs during homeostasis, they are efficiently activated to self-renew in response to bone marrow injury or G-CSF stimulation. After re-establishment of homeostasis, activated HSCs return to dormancy, suggesting that HSCs are not stochastically entering the cell cycle but reversibly switch from dormancy to self-renewal under conditions of hematopoietic stress.