From the Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine (A.L., S.B., L.D., L.H.), Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine (A.L., M.M., C.B.), and BIOSS Centre for Biological Signaling Studies (L.H.), University of Freiburg, Germany.
Arterioscler Thromb Vasc Biol. 2018 Mar;38(3):566-574. doi: 10.1161/ATVBAHA.117.310549. Epub 2018 Jan 4.
Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome.
We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors. We found an overrepresentation of corresponding transcription factor binding motifs within the promotor region of EC-enriched genes, suggesting that they control the EC transcriptome. Cardiac ECs exhibit a distinct gene expression profile when compared with renal, cerebral, or pulmonary ECs. For example, we found the /, and signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis.
The results from this study provide a comprehensive resource of gene expression and transcriptional control in cardiac ECs. The cardiac EC transcriptome exhibits distinct differences in gene expression compared with other cardiac cell types and ECs from other organs. We identified new candidate genes that have not been investigated in ECs yet as promising targets for future evaluation.
内皮细胞(ECs)是一种高度特化的细胞类型,不同器官或血管床之间存在明显的多样性。心脏内皮细胞是心脏生理学和病理生理学的重要参与者,但尚未充分表征。因此,本研究旨在分析心脏 EC 的转录组。
我们应用荧光辅助细胞分选技术从成年小鼠心脏中分离出纯 ECs。RNAseq 揭示了 1288 个基因在心脏 EC 中表达明显高于心脏组织,包括几个转录因子。我们在 EC 富集基因的启动子区域内发现了相应转录因子结合基序的过度表达,这表明它们控制着 EC 的转录组。与肾脏、大脑或肺 EC 相比,心脏 EC 表现出明显不同的基因表达谱。例如,我们发现心脏 EC 中表达较高的 /, 和 信号级联,这是脂肪酸摄取的关键调节剂,参与动脉粥样硬化的发生。
本研究的结果为心脏 EC 中的基因表达和转录调控提供了全面的资源。与其他心脏细胞类型和其他器官的 EC 相比,心脏 EC 的转录组在基因表达上表现出明显的差异。我们确定了一些尚未在 EC 中研究过的新候选基因,它们可能是未来评估的有前途的靶点。