Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation
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DOI：
10.7554/elife.51413
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发表时间：
2020-01-16
期刊：
影响因子：
7.7
通讯作者：
Rehman, Jalees
中科院分区：
文献类型：
--
作者：
Jambusaria, Ankit;Hong, Zhigang;Rehman, Jalees
血管内衬内皮细胞从事不同的器官特异性功能，但很少有人知道他们的特征基因表达谱。脑、肺和心脏内皮翻译组的RNA测序鉴定了在每个器官的内皮中表达的特定途径、转运蛋白和细胞表面标志物，其可以在http://www.rehmanlab.org/ribo上可视化。我们发现内皮细胞表达通常在周围组织中发现的基因，例如脑内皮中的突触囊泡基因和心脏内皮中的心脏收缩基因。内皮单细胞RNA-Seq数据的互补分析鉴定了跨内皮翻译组和单细胞转录组共享的分子特征。内皮细胞的组织特异性异质性在全身性体内炎性损伤过程中得以维持，如对炎性刺激的不同反应所证明的。我们的研究定义了内皮异质性和可塑性，并提供了一个分子框架，以了解器官特异性血管疾病的机制和治疗靶向个别血管床。
Blood vessels are lined by endothelial cells engaged in distinct organ-specific functions but little is known about their characteristic gene expression profiles. RNA-Sequencing of the brain, lung, and heart endothelial translatome identified specific pathways, transporters and cell-surface markers expressed in the endothelium of each organ, which can be visualized at http://www.rehmanlab.org/ribo. We found that endothelial cells express genes typically found in the surrounding tissues such as synaptic vesicle genes in the brain endothelium and cardiac contractile genes in the heart endothelium. Complementary analysis of endothelial single cell RNA-Seq data identified the molecular signatures shared across the endothelial translatome and single cell transcriptomes. The tissue-specific heterogeneity of the endothelium is maintained during systemic in vivo inflammatory injury as evidenced by the distinct responses to inflammatory stimulation. Our study defines endothelial heterogeneity and plasticity and provides a molecular framework to understand organ-specific vascular disease mechanisms and therapeutic targeting of individual vascular beds.