Evaluation of the long-term reconstituting subset of hematopoietic stem cells with CD150.

Evaluation of the long-term reconstituting subset of hematopoietic stem cells with CD150.
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DOI:
10.1002/stem.170
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发表时间:
2009-10
期刊:
影响因子:
5.2
通讯作者:
Weissman, Irving L.
Weissman, Irving L.
中科院分区:
医学2区
文献类型:
--
作者:
Papathanasiou, Peter;Attema, Joanne L.;Karsunky, Holger;Xu, Jian;Smale, Stephen T.;Weissman, Irving L.

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血液是一种细胞周转率很高的组织,在胎儿个体发育过程中从肝脏种植的骨髓造血干细胞(HSCs)不断地补充血液。在这里,我们证明了cKit+Thy1.1(Lo)Lin(-/lo)Sca1+Flk2-造血干细胞的长期(LT)重组亚群是CD150+。来源于胎肝的HSCs从E14.5开始表现出长期的多系植入,CD150细胞表面分子可以很容易地替代Thy1.1作为LT-HSCs在该组织中的阳性标记。在胎肝和成人骨髓中,cKit+Thy1.1(Lo)Lin(-/lo)Sca1+Flk2-CD150+细胞均表现出较强的LT竞争性植入、自我更新、多向分化能力,以及可获得的染色质构型,与纯化细胞亚群中红系/巨核系基因的高表达相一致。我们的数据表明,通过适当的细胞表面标记组合,干细胞可以准确地分离到高纯度并进行鉴定。这对于澄清谱系关系和鉴定正常组织和肿瘤组织中干细胞自我更新和分化的真正调节者是重要的。
Blood is a tissue with a high cell turnover rate that is constantly being replenished by bone marrow hematopoietic stem cells (HSCs) seeded during fetal ontogeny from the liver. Here we show that the long-term (LT) reconstituting subset of cKit+Thy1.1(lo)Lin(-/lo)Sca1+Flk2- hematopoietic stem cells is CD150+. HSCs sourced from the fetal liver show long-term, multilineage engraftment from E14.5 onwards, and the CD150 cell surface molecule can readily substitute Thy1.1 as a positive marker of LT-HSCs in this tissue. From both fetal liver and adult bone marrow, cKit+Thy1.1(lo)Lin(-/lo)Sca1+Flk2-CD150+ cells exhibit robust LT competitive engraftment, self-renewal, multilineage differentiation capacity, and an accessible chromatin configuration consistent with high expression of erythroid/megakaryoid genes in purified cell subsets. Our data demonstrate that with appropriate combinations of cell surface markers, stem cells can be accurately isolated to high purity and characterized. This is important for the clarification of lineage relationships and the identification of bona fide regulators of stem cell self-renewal and differentiation, both in normal and neoplastic tissues.
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