Genome-wide identification of endothelial cell-enriched genes in the mouse embryo
Genome-wide identification of endothelial cell-enriched genes in the mouse embryo
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DOI：
10.1182/blood-2011-12-398156
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发表时间：
2012-07-26
期刊：
影响因子：
20.3
通讯作者：
Ema, Masatsugu
中科院分区：
文献类型：
--
作者：
Takase, Haruka;Matsumoto, Ken;Ema, Masatsugu
哺乳动物胚胎和卵黄囊的早期血管是由新生血管母细胞聚集成原始血管丛，然后经历复杂的重塑过程而发育的。血管生成对成人疾病进展也很重要。然而，血管发育的确切分子机制仍不清楚。因此，确定哪些基因在发育中的内皮细胞（EC）中特异性表达是非常有意义的。在这里，我们使用Flk 1缺陷的小鼠胚胎，缺乏内皮细胞，进行全基因组调查与血管发育相关的基因。我们确定了184个基因，这些基因在发育中的EC中高度富集。这些基因中的大多数的人类直系同源物也在HUVEC中表达，并且对22个人类直系同源物的小干扰RNA敲低实验表明，这些基因中的6个在HUVEC的管形成中起作用。此外，我们通过基因靶向方法创建了Arhgef 15敲除和RhoJ敲除小鼠，发现Arhgef 15和RhoJ对新生儿视网膜血管化很重要。因此，在我们的调查中发现的基因显示高表达的EC，这些基因的进一步分析，应有助于我们了解的分子机制的血管发育的小鼠。（血。2012;120（4）：914-923）
The early blood vessels of the embryo and yolk sac in mammals develop by aggregation of de novo-forming angio-blasts into a primitive vascular plexus, which then undergoes a complex remodeling process. Angiogenesis is also important for disease progression in the adult. However, the precise molecular mechanism of vascular development remains unclear. It is therefore of great interest to determine which genes are specifically expressed in developing endothelial cells (ECs). Here, we used Flk1-deficient mouse embryos, which lack ECs, to perform a genome-wide survey for genes related to vascular development. We identified 184 genes that are highly enriched in developing ECs. The human orthologs of most of these genes were also expressed in HUVECs, and small interfering RNA knockdown experiments on 22 human orthologs showed that 6 of these genes play a role in tube formation by HUVECs. In addition, we created Arhgef15 knockout and RhoJ knockout mice by a gene-targeting method and found that Arhgef15 and RhoJ were important for neonatal retinal vascularization. Thus, the genes identified in our survey show high expression in ECs; further analysis of these genes should facilitate our understanding of the molecular mechanisms of vascular development in the mouse. (Blood. 2012;120(4):914-923)