S1PR1型
细胞生物学
G蛋白偶联受体
生物
人口
鞘氨醇-1-磷酸受体
鞘氨醇
淋巴管新生
转录组
内皮干细胞
淋巴管内皮
内皮
信号转导
受体
1-磷酸鞘氨醇
免疫学
淋巴系统
基因表达
癌症研究
内分泌学
医学
基因
遗传学
血管内皮生长因子A
癌症
体外
血管内皮生长因子
环境卫生
转移
血管内皮生长因子受体
作者
Eric Engelbrecht,Michel V. Levesque,Liqun He,Michael Vanlandewijck,Anja Nitzsche,Hira Niazi,Andrew Kuo,Sasha A Singh,Masamichi Aikawa,Kristina M. Holton,Richard L. Proia,Mari Kono,William T. Pu,Eric Camerer,Christer Betsholtz,Timothy Hla
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2020-02-24
卷期号:9
被引量:30
摘要
Despite the medical importance of G protein-coupled receptors (GPCRs), in vivo cellular heterogeneity of GPCR signaling and downstream transcriptional responses are not understood. We report the comprehensive characterization of transcriptomes (bulk and single-cell) and chromatin domains regulated by sphingosine 1-phosphate receptor-1 (S1PR1) in adult mouse aortic endothelial cells. First, S1PR1 regulates NFκB and nuclear glucocorticoid receptor pathways to suppress inflammation-related mRNAs. Second, S1PR1 signaling in the heterogenous endothelial cell (EC) subtypes occurs at spatially-distinct areas of the aorta. For example, a transcriptomically distinct arterial EC population at vascular branch points (aEC1) exhibits ligand-independent S1PR1/ß-arrestin coupling. In contrast, circulatory S1P-dependent S1PR1/ß-arrestin coupling was observed in non-branch point aEC2 cells that exhibit an inflammatory gene expression signature. Moreover, S1P/S1PR1 signaling regulates the expression of lymphangiogenic and inflammation-related transcripts in an adventitial lymphatic EC (LEC) population in a ligand-dependent manner. These insights add resolution to existing concepts of endothelial heterogeneity, GPCR signaling and S1P biology.
科研通智能强力驱动
Strongly Powered by AbleSci AI