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Blood stem cells emerge from aortic endothelium by a novel type of cell transition

机译:血液干细胞通过一种新型的细胞过渡方式从主动脉内皮中产生

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摘要

The ontogeny of haematopoietic stem cells (HSCs) during embryonic development is still highly debated, especially their possible lineage relationship to vascular endothelial cells. The first anatomical site from which cells with long-term HSC potential have been isolated is the aorta-gonad-mesonephros (AGM), more specifically the vicinity of the dorsal aortic floor. But although some authors have presented evidence that HSCs may arise directly from the aortic floor into the dorsal aortic lumen, others support the notion that HSCs first emerge within the underlying mesenchyme. Here we show by non-invasive, high-resolution imaging of live zebrafish embryos, that HSCs emerge directly from the aortic floor, through a stereotyped process that does not involve cell division but a strong bending then egress of single endothelial cells from the aortic ventral wall into the sub-aortic space, and their concomitant transformation into haematopoietic cells. The process is polarized not only in the dorso-ventral but also in the rostro-caudal versus medio-lateral direction, and depends on Runx1 expression: in Runx1-deficient embryos, the exit events are initially similar, but much rarer, and abort into violent death of the exiting cell. These results demonstrate that the aortic floor is haemogenic and that HSCs emerge from it into the sub-aortic space, not by asymmetric cell division but through a new type of cell behaviour, which we call an endothelial haematopoietic transition.
机译:造血干细胞(HSCs)在胚胎发育过程中的个体存在仍备受争议,尤其是它们与血管内皮细胞的可能谱系关系。从中分离出具有长期HSC潜能的细胞的第一个解剖部位是主动脉-性腺-中肾(AGM),更具体地说是背主动脉底部附近。但是,尽管一些作者已经提供了证据表明HSC可能直接从主动脉底升入背主动脉腔,但其他人支持HSC首先出现在下层间充质中的观点。在这里,我们通过活斑马鱼胚胎的非侵入性高分辨率成像显示,HSC通过不涉及细胞分裂而是强烈弯曲然后从主动脉腹腔流出的单个内皮细胞的定型过程直接从主动脉底部出现壁进入主动脉下腔,并随之转化为造血细胞。该过程不仅在背腹间极化,而且在Rotro-caudal相对于中外侧也极化,并且取决于Runx1的表达:在Runx1缺陷的胚胎中,退出事件最初是相似的,但更罕见,并终止于退出细胞的暴力死亡。这些结果表明,主动脉底是造血的,并且HSC不是通过不对称的细胞分裂而是通过一种新型的细胞行为,从内皮细胞进入主动脉下腔,我们称之为内皮型造血过渡。

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  • 来源
    《Nature》 |2010年第7285期|112-115|共4页
  • 作者单位

    Institut Pasteur, Unite Macrophages et Developpement de I'lmmunite and CNRS: URA2578, 25 rue du Dr Roux, F-75724 Paris CEDEX 15, France;

    Institut Pasteur, Unite Macrophages et Developpement de I'lmmunite and CNRS: URA2578, 25 rue du Dr Roux, F-75724 Paris CEDEX 15, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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