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Single-cell transcriptional profiling of aortic endothelium identifies a hierarchy from endovascular progenitors to differentiated cells

Abstract

The cellular and molecular profiles that govern the endothelial heterogeneity of the circulatory system have yet to be elucidated. Using a data-driven approach to study the endothelial compartment via single-cell RNA sequencing, we characterized cell subpopulations within and assigned them to a defined endothelial hierarchy. We show that two transcriptionally distinct endothelial populations exist within the aorta and, using two independent trajectory analysis methods, confirm that they represent transitioning cells rather than discrete cell types. Gene co-expression analysis revealed crucial regulatory networks underlying each population, including significant metabolic gene networks in progenitor cells. Using mitochondrial activity assays and phenotyping, we confirm that endovascular progenitors display higher mitochondrial content compared to differentiated endothelial cells. The identities of these populations were further validated against bulk RNA sequencing (RNA-seq) data obtained from normal and tumor-derived vasculature. Our findings validate the heterogeneity of the aortic endothelium and previously suggested hierarchy between progenitor and differentiated cells.

Type Journal
Authors Lukowski, S. W.; Patel, J.; Andersen, S. B.; Sim, S. L.; Wong, H. Y.; Tay, J.; Winkler, I.; Powell, J. E.; Khosrotehrani, K.
Responsible Garvan Author A/Prof Joseph Powell
Publisher Name Cell Reports
Published Date 2019-05-01
Published Volume 27
Published Issue 9
Published Pages 2748-2758.e3
Status Published in-print
DOI 10.1016/j.celrep.2019.04.102
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31141696