THE LONG-TERM REPOPULATING SUBSET OF HEMATOPOIETIC STEM-CELLS IS DETERMINISTIC AND ISOLATABLE BY PHENOTYPE

THE LONG-TERM REPOPULATING SUBSET OF HEMATOPOIETIC STEM-CELLS IS DETERMINISTIC AND ISOLATABLE BY PHENOTYPE
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DOI:
10.1016/1074-7613(94)90037-x
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发表时间:
1994-11-01
期刊:
影响因子:
32.4
通讯作者:
WEISSMAN, IL
WEISSMAN, IL
中科院分区:
医学1区
文献类型:
--
作者:
MORRISON, SJ;WEISSMAN, IL

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Thy-1.1(lo)Sca-1(hi)Lin(-/lo)群体(占C57 BL/Ka-Thy-1.1骨髓的0.05%)高度富集造血干细胞,包括该小鼠品系中的所有多能祖细胞;然而,该组分的功能重建活性是异质的。只有大约25%的克隆重建的细胞从这个人口是长期的,其余的克隆产生短暂的多谱系重建。通过基于谱系标志物表达的分级,Thy-1.1(lo)Sca-1(hi)Lin(-/lo)群体已被分解为三个亚群:Lin(-)Mac-1(-)CD 4(-); Lin-Mac(-1lo)CD 4(-);和Mac-1(lo)CD 4(lo)。其中,只有Lin(-)Mac-1-CD 4(-)群体高度富集长期重建造血干细胞。瞬时和长期多能祖细胞的比较表明,长期祖细胞具有较少的CFU-S活性,具有相同的辐射防护性,并且在细胞周期中的频率较低。基于谱系标志物表达预测重建寿命的能力表明重建潜力是确定性的,而不是随机的。
The Thy-1.1(lo)Sca-1(hi)Lin(-/lo) population, representing 0.05% of C57BL/Ka-Thy-1.1 bone marrow, is highly enriched for hematopoietic stem cells and includes all multipotent progenitors in this mouse strain; however, the functional reconstituting activity of this fraction is heterogeneous. Only around 25% of clonal reconstitutions by cells from this population are long term; remaining clones yield transient multilineage reconstitutions. By fractionating based on lineage marker expression, the Thy-1.1(lo)Sca-1(hi)Lin(-/lo) population has been resolved into three subpopulations: Lin(-)Mac-1(-)CD4(-); Lin-Mac(-1lo)CD4(-); and Mac-1(lo)CD4(lo). Of these, only the Lin(-)Mac-1-CD4(-) population is highly enriched for long-term reconstituting hematopoietic stem cells. A comparison of transient and long-term multipotent progenitors indicates that long-term progenitors have less CFU-S activity, are equally radioprotective, and are less frequently in cell cycle. The ability to predict the longevity of reconstitution based on lineage marker expression indicates that reconstitution potential is deterministic, not stochastic.