Abstract
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.
Highlights
Endothelial cells (ECs) line blood vessels in all tissues and organs, and they form a barrier which tightly regulates the trafficking of oxygen, metabolites, small molecules and immune cells into the respective tissue (Liao, 2013)
Log fold change values were calculated between endothelial mRNA versus whole tissue mRNA using quantitative PCR
The differential expression analysis was concordant with the Principal component analysis (PCA) and identified 1692 genes which were differentially expressed in brain ECs, 1052 genes which were differentially expressed in lung ECs, and 570 genes which were differentially expressed in heart ECs (Figure 1B)
Summary
Endothelial cells (ECs) line blood vessels in all tissues and organs, and they form a barrier which tightly regulates the trafficking of oxygen, metabolites, small molecules and immune cells into the respective tissue (Liao, 2013). Jambusaria et al show that brain, heart, and lung endothelial cells have distinct genetic signatures. To understand further the variegated nature of the endothelium, we used the RiboTag transgenic mouse model, in which LoxP mice express an HA-tag on the ribosomal Rpl protein (Sanz et al, 2009) These mice enable direct isolation of tissue-specific mRNAs. undergoing translation without cell disassociation (Sanz et al, 2009). To allow other researchers to explore the organ-specific EC translatome heterogeneity, we have generated a searchable database (http://www.rehmanlab.org/ribo), in which users can visualize gene expression levels of individual genes
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