Locational memory of macrovessel vascular cells is transcriptionally imprinted

The locational predisposition of vascular pathologies illustrates the need for a better insight into vascular heterogeneity. To investigate the transcriptomic basis of angiodiversity, we isolated and analyzed transcriptomes from endothelial cells and vascular smooth muscle cells from nine different adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We identified both reported and novel expression patterns defining specialized adult blood vessels. Our findings also show that adult vascular cells in culture express a remarkably high number of transcription factors crucial to organ development in the embryo. The persistent expression of these genes in culture indicates that these genes are not regulated by the flow or surrounding cell types but are rather fixed in the molecular memory. Therefore, our findings prompt the re-thinking of the extrapolation of results from single-origin endothelial cell systems. Overall design: Whole transcriptome data of primary adult canine endothelial and vascular smooth muscle cells of 9 macrovessels, produced on Illumina NextSeq500 using a single-end 75 bp configuration

血管病变的部位易感性凸显了深入解析血管异质性的必要性。为探究血管多样性的转录组学基础，我们从9种不同的成年犬类大血管中分离并分析了内皮细胞（endothelial cells）与血管平滑肌细胞（vascular smooth muscle cells）的转录组（transcriptome），所涉血管包括主动脉、冠状动脉、腔静脉、门静脉、股动脉、股静脉、隐静脉、肺静脉与肺动脉。本研究鉴定出了可界定特异性成年血管的既有报道表达模式与全新表达特征；同时发现，体外培养的成年血管细胞可大量表达对胚胎器官发育至关重要的转录因子（transcription factors）。这些基因在培养条件下的持续表达表明，其调控不受血流或周围细胞类型的影响，而是固化于分子记忆之中。因此，本研究结果提示，需重新审视基于单一来源内皮细胞系统所得研究结果的外推适用性。整体实验设计：针对9种犬类大血管的原代成年内皮细胞与血管平滑肌细胞的全转录组数据，采用Illumina NextSeq500测序平台，以单端75bp的测序配置完成测序。