Endothelial cell diversity revealed by global expression profiling

Endothelial cell diversity revealed by global expression profiling
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DOI:
10.1073/pnas.1434429100
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发表时间:
2003-09-16
影响因子:
11.1
通讯作者:
Brown, PO
Brown, PO
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chi, JT;Chang, HY;Brown, PO

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血管系统是局部专门化的,以适应广泛变化的血流和压力以及个体组织的不同需求。排列在血管和淋巴管内腔的内皮细胞(EC)在血管结构和生理学的区域特化中起着不可或缺的作用。然而,我们对欧盟多样性的理解是有限的。为了在全球范围内探索EC的专业化,我们使用DNA微阵列来确定53个培养EC的表达谱。我们发现,不同血管的内皮细胞和不同组织的微血管内皮细胞具有不同的和特征性的基因表达谱。基因表达模式的普遍差异将大血管EC与微血管EC区分开来。我们确定了动脉和静脉内皮细胞的基因组特征。Hey 2是斑马鱼基因gridlock的人类同源物,在动脉EC中选择性表达,并诱导几种动脉特异性基因的表达。在建立左/右不对称的几个关键基因表达优先在静脉内皮细胞,表明血管分化和身体计划发展之间的协调。不同组织微血管内皮细胞中的组织特异性表达模式表明它们是不同的分化细胞类型,在其各自器官和组织的局部生理学中发挥作用。
The vascular system is locally specialized to accommodate widely varying blood flow and pressure and the distinct needs of individual tissues. The endothelial cells (ECs) that line the lumens of blood and lymphatic vessels play an integral role in the regional specialization of vascular structure and physiology. However, our understanding of EC diversity is limited. To explore EC specialization on a global scale, we used DNA microarrays to determine the expression profile of 53 cultured ECs. We found that ECs from different blood vessels and microvascular ECs from different tissues have distinct and characteristic gene expression profiles. Pervasive differences in gene expression patterns distinguish the ECs of large vessels from microvascular ECs. We identified groups of genes characteristic of arterial and venous endothelium. Hey2, the human homologue of the zebrafish gene gridlock, was selectively expressed in arterial ECs and induced the expression of several arterial-specific genes. Several genes critical in the establishment of left/right asymmetry were expressed preferentially in venous ECs, suggesting coordination between vascular differentiation and body plan development. Tissue-specific expression patterns in different tissue microvascular ECs suggest they are distinct differentiated cell types that play roles in the local physiology of their respective organs and tissues.