CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.

CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.
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DOI:
10.1007/s10456-011-9251-z
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发表时间:
2012-03
期刊:
影响因子:
9.8
通讯作者:
Schlingemann, Reinier O.
Schlingemann, Reinier O.
中科院分区:
医学1区
文献类型:
--
作者:
Siemerink, Martin J.;Klaassen, Ingeborg;Vogels, Ilse M. C.;Griffioen, Arjan W.;Van Noorden, Cornelis J. F.;Schlingemann, Reinier O.

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静止的内皮细胞向末端细胞迁移和跟踪增殖细胞的功能转变是萌芽血管生成过程中的一个关键事件。我们以前发现唾液粘蛋白CD34在培养的一小部分内皮细胞中表达,这些细胞延伸丝状足突:体内TIP细胞的标志。在本研究中,我们研究了在体外培养的内皮单层中表达CD34的内皮细胞。我们发现,与CD34阴性的细胞相比,CD34阳性的人脐静脉内皮细胞表现出低的增殖活性和所有已知的TIP细胞标志物的mRNA表达增加。对CD34阳性内皮细胞的全基因组信使核糖核酸图谱分析显示,与血管生成和迁移相关的生物学功能丰富,而CD34阴性内皮细胞的增殖相关功能丰富。此外,我们还发现,在体外,CD34阳性细胞在暴露于分别增加或限制体内TIP细胞数量的刺激时会增加或减少。我们的发现表明,在血管内皮细胞培养中存在具有TIP细胞几乎所有已知特性的细胞,并且可以根据CD34的表达来分离它们。这一新的策略可能会为未来研究TIP细胞在血管生成中的分子过程和功能开辟新的途径。本文的在线版本(doi:10.1007/s10456-0119251-z)包含补充材料,授权用户可以使用。
The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis. The online version of this article (doi:10.1007/s10456-011-9251-z) contains supplementary material, which is available to authorized users.
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