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Cell:骨髓干细胞的活性周期

来源:生物通 2009-01-08 14:45

专题:Cell专题

骨髓造血干细胞是生物体内维持血细胞更新的重要细胞系。尽管,骨髓造血干细胞分化的频率很低,但是科学家们认为骨髓造血干细胞库常数星期更新一次,这表明骨髓造血干细胞很有规律地进入或是退出细胞周期。

在本研究中,科学家使用流式细胞计数技术(带有BrdU and histone H2B-GFP标签)鉴定出小鼠的休眠骨髓造血干细胞(dormant mouse bone marrow hematopoietic stem cells, d-HSC),表现为lin-Sca1+cKit+CD150+CD48-CD34- 。

用计算机模型预测得出结论,这些休眠的骨髓造血干细胞每145天自我更新一次,在它整个生命周期里共更新5次。休眠的骨髓造血干细胞具有多种自我更新的活性。在内环境维持稳定的情况下,休眠的骨髓造血干细胞继续保持休眠状态,当骨髓受到损伤或是在G-CSF的刺激下,骨髓造血干细胞又恢复自我更新的活力。分化出新的血液细胞维持内环境的稳态,活跃分化后的造血干细胞在生命周期内在此回归到休眠状态。

这些研究结果表明,骨髓造血干细胞一般处于休眠状态,只有出现造血压力的时候才会被激活,产生自我更新的能力。(生物谷Bioon.com)

生物谷推荐原始出处:

Cell, 04 December 2008 doi:10.1016/j.cell.2008.10.048

Hematopoietic Stem Cells Reversibly Switch from Dormancy to Self-Renewal during Homeostasis and Repair

Anne Wilson3,Elisa Laurenti1,8,Gabriela Oser1,8,Richard C. van der Wath4,8,William Blanco-Bose1,8,Maike Jaworski1,Sandra Offner1,Cyrille F. Dunant6,Leonid Eshkind5,Ernesto Bockamp5,Pietro Lió4,H. Robson MacDonald3andAndreas Trumpp1,2,7,,

1 Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, CH-1015 Lausanne, Switzerland
2 Divison of Cell Biology, Deutsches Krebsforschungszentrum (DKFZ), Division of Cell Biology, DKFZ-ZMBH Alliance,Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
3 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland
4 Computer Laboratory, University of Cambridge, Cambridge CB3 0FD, UK
5 Institute for Toxicology, Laboratory of Molecular Mouse Genetics, Johannes Gutenberg-University Mainz, 55113 Mainz, Germany
6 LMC-IMX and Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
7 Heidelberg Institute for Stem Cell Technologies and Experimental Medicine (HI-STEM), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
8 These authors contributed equally to this work

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 linSca1+cKit+CD150+CD48CD34 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.

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