Abstract
Endothelial-to-mesenchymal transition (EndoMT), a specific form of epithelial-to-mesenchymal transition, drives a growing number of human (Homo sapiens) pathological conditions. This emerging knowledge opens a path to discovering novel therapeutic targets for many EndoMT-associated disorders. Here, we constructed an atlas of the endothelial-cell transcriptome and demonstrated EndoMT-induced global changes in transcriptional gene expression. Our gene ontology analyses showed that EndoMT could be a specific checkpoint for leukocyte chemotaxis, adhesion, and transendothelial migration. We also identified distinct gene expression signatures underlying EndoMT across arterial, venous, and microvascular endothelial cells. We performed protein-protein interaction network analyses, identifying a class of highly connected hub genes in endothelial cells from different vascular beds. Moreover, we found that the short-chain fatty acid acetate strongly inhibits the transcriptional program of EndoMT in endothelial cells from different vascular beds across tissues. Our results reveal the molecular signature and cell-type difference of EndoMT across distinct tissue- and vascular-bed-specific endothelial cells, providing a powerful discovery tool and resource value. These results suggest that therapeutically manipulating the endothelial transcriptome could treat an increasing number of EndoMT-associated pathological conditions.