Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.

Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.
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表皮生长因子样结构域7是内皮谱系和活性血管生成的标记。

DOI:
10.1002/dvg.22781
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发表时间:
2014-07
期刊:
影响因子:
1.5
通讯作者:
Stuhlmann, Heidi
Stuhlmann, Heidi
中科院分区:
生物学4区
文献类型:
--
作者:
Bambino, Kathryn;Lacko, Lauretta A.;Hajjar, Katherine A.;Stuhlmann, Heidi

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表皮生长因子样域7(Egfl7)在发育中的胚胎中的表达主要局限于血管母细胞/血管母细胞的中胚层前体细胞和血管内皮细胞。我们推测,Egfl7标志着胚胎发育过程中的内皮谱系,可以用来定义内皮祖细胞的出现,也可以用来显示胚胎中新形成的血管以及成人生理和病理血管生成的过程。我们已经产生了一种转基因小鼠,它在最小的Egfl7调控序列(Egfl7:EGFP)的控制下表达增强的绿色荧光蛋白(EGFP)。转基因的表达与内源Egfl7在尿囊、卵黄囊和胚胎本身的血管生成和血管生成部位的表达相似。转基因在大多数成体器官静止的内皮细胞中不表达。然而,子宫和卵巢在整个发情周期中经历了血管生长和重塑,表达了高水平的Egfl7:EGFP。重要的是,Egfl7:EGFP转基因在成年新生血管中得到了诱导表达。我们还发现,Egfl7表达的增加有助于小鼠视网膜的病理性血管重建。据我们所知,这是第一个能够监测血管生成活跃部位和血管生成部位的内皮细胞的小鼠模型。该模型还有助于通过荧光激活细胞分选(FACS)分离和鉴定EGFL7+内皮细胞群。综上所述,我们的结果表明Egfl7:EGFP报告小鼠是一个有价值的工具,可以用来阐明血管在发育过程中和病理情况下形成的机制。
Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo is largely restricted to sites of mesodermal progenitors of angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that Egfl7 marks the endothelial lineage during embryonic development, and can be used to define the emergence of endothelial progenitor cells, as well as to visualize newly forming vasculature in the embryo and during the processes of physiological and pathological angiogenesis in the adult. We have generated a transgenic mouse strain that expresses enhanced green fluorescent protein (eGFP) under the control of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene recapitulated that of endogenous Egfl7 at sites of vasculogenesis and angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene was not expressed in the quiescent endothelium of most adult organs. However, the uterus and ovary, which undergo vascular growth and remodeling throughout the estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the Egfl7:eGFP transgene was induced in adult neovasculature. We also found that increased Egfl7 expression contributed to pathological revascularization in the mouse retina. To our knowledge, this is first mouse model that enables monitoring endothelial cells at sites of active vasculogenesis and angiogenesis. This model also facilitated the isolation and characterization of EGFL7+ endothelial cell populations by fluorescence activated cell sorting (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a valuable tool that can be used to elucidate the mechanisms by which blood vessels form during development and under pathologic circumstances.
DOI: 10.1371/journal.pone.0012156
发表时间: 2010-08-16
期刊: PloS one
影响因子: 3.7
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