骨髓造血干細(xì)胞是生物體內(nèi)維持血細(xì)胞更新的重要細(xì)胞系。盡管,，骨髓造血干細(xì)胞分化的頻率很低,，但是科學(xué)家們認(rèn)為骨髓造血干細(xì)胞庫(kù)常數(shù)星期更新一次，這表明骨髓造血干細(xì)胞很有規(guī)律地進(jìn)入或是退出細(xì)胞周期,。
在本研究中,，科學(xué)家使用流式細(xì)胞計(jì)數(shù)技術(shù)（帶有BrdU and histone H2B-GFP標(biāo)簽）鑒定出小鼠的休眠骨髓造血干細(xì)胞（dormant mouse bone marrow hematopoietic stem cells， d-HSC）,，表現(xiàn)為lin-Sca1+cKit+CD150+CD48-CD34- ,。
用計(jì)算機(jī)模型預(yù)測(cè)得出結(jié)論，這些休眠的骨髓造血干細(xì)胞每145天自我更新一次,，在它整個(gè)生命周期里共更新5次,。休眠的骨髓造血干細(xì)胞具有多種自我更新的活性。在內(nèi)環(huán)境維持穩(wěn)定的情況下,，休眠的骨髓造血干細(xì)胞繼續(xù)保持休眠狀態(tài),，當(dāng)骨髓受到損傷或是在G-CSF的刺激下，骨髓造血干細(xì)胞又恢復(fù)自我更新的活力,。分化出新的血液細(xì)胞維持內(nèi)環(huán)境的穩(wěn)態(tài),，活躍分化后的造血干細(xì)胞在生命周期內(nèi)在此回歸到休眠狀態(tài)。
這些研究結(jié)果表明,，骨髓造血干細(xì)胞一般處于休眠狀態(tài),，只有出現(xiàn)造血壓力的時(shí)候才會(huì)被激活，產(chǎn)生自我更新的能力,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
