Cardiac Endothelial Cell Transcriptome
Cardiac Endothelial Cell Transcriptome
复制标题
DOI：
10.1161/atvbaha.117.310549
复制
发表时间：
2018-03-01
影响因子：
8.7
通讯作者：
Hein, Lutz
中科院分区：
文献类型：
--
作者：
Lother, Achim;Bergemann, Stella;Hein, Lutz
目的内皮细胞是一种高度特化的细胞类型，在不同的器官或血管床之间具有显著的多样性。心脏EC在心脏生理学和病理生理学中是重要的参与者，但尚未得到充分表征。因此，本研究的目的是分析心脏EC transcriptome.Approach和结果，我们应用荧光辅助细胞分选分离纯内皮细胞从成年小鼠心脏。RNAseq揭示了1288个基因主要在心脏EC与心脏组织中表达，包括几个转录因子。我们发现了EC富集基因的启动子区域内相应的转录因子结合基序的过度表达，表明它们控制EC转录组。与肾、脑或肺EC相比，心脏EC表现出不同的基因表达谱。例如，我们发现Meox 2/Tcf 15，Fabp 4和Cd 36信号级联在心脏EC中高表达，这是脂肪酸摄取的关键调节因子，并参与动脉粥样硬化的发展。结论本研究的结果提供了心脏EC中基因表达和转录调控的综合资源。与其他心脏细胞类型和来自其他器官的EC相比，心脏EC转录组在基因表达方面表现出明显的差异。我们确定了尚未在EC中研究的新候选基因，作为未来评估的有希望的靶点。
Objective 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.Approach and Results 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 Meox2/Tcf15, Fabp4, and Cd36 signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis.Conclusions 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.