Shin Donghun, Anderson David J
Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA.
Dev Dyn. 2005 Aug;233(4):1589-604. doi: 10.1002/dvdy.20479.
Arteries are distinguished from veins by differences in gene expression, as well as in their anatomy and physiology. The characterization of arterial- and venous-specific genes may improve our understanding of cardiovascular development and disease. Here we report the results of a subtractive hybridization screen for arterial-specific genes, and describe in detail the expression of a novel arterial-specific gene, Depp (decidual protein induced by progesterone), using a GFP-Cre knock-in that permits a comparison of both instantaneous and cumulative expression patterns in situ. Several features of Depp expression are noteworthy. First, Depp is expressed in endothelial cells of peripheral tissues, but not in atrial or ventricular endocardial cells of the heart. Very few genes have been reported to discriminate between these two cell types, and therefore this specificity may be useful in generating conditional mutations in other genes implicated in cardiovascular development. Second, Depp reveals an unexpected degree of molecular heterogeneity among arterial endothelial cells. Third, Depp is up-regulated in subsets of endothelial cells, in settings of adult neo-vascularization, including tumor angiogenesis. Taken together, these data reveal unanticipated temporal and spatial heterogeneity among arterial endothelial cells of various tissues and organs, raising new questions regarding the functional significance of this diversity.
动脉与静脉在基因表达、解剖结构和生理功能上存在差异。对动脉和静脉特异性基因的表征可能会增进我们对心血管发育和疾病的理解。在此，我们报告了一项针对动脉特异性基因的消减杂交筛选结果，并详细描述了一种新型动脉特异性基因Depp（孕酮诱导的蜕膜蛋白）的表达情况，该基因利用GFP-Cre基因敲入技术，能够原位比较瞬时和累积表达模式。Depp表达的几个特征值得注意。首先，Depp在外周组织的内皮细胞中表达，但在心脏的心房或心室心内膜细胞中不表达。据报道，很少有基因能够区分这两种细胞类型，因此这种特异性可能有助于在涉及心血管发育的其他基因中产生条件性突变。其次，Depp揭示了动脉内皮细胞之间意想不到的分子异质性程度。第三，在包括肿瘤血管生成在内的成人新血管形成情况下，Depp在内皮细胞亚群中上调。综上所述，这些数据揭示了各种组织和器官的动脉内皮细胞之间意想不到的时空异质性，引发了关于这种多样性功能意义的新问题。
