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Cell Rep. 2019 May 28;27(9):2748-2758.e3. doi: 10.1016/j.celrep.2019.04.102.

Single-Cell Transcriptional Profiling of Aortic Endothelium Identifies a Hierarchy from Endovascular Progenitors to Differentiated Cells.

Author information

1
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
2
The University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia.
3
Faculty of Medicine, Translational Research Institute, Mater Research Institute-The University of Queensland, Woolloongabba, QLD 4102, Australia.
4
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales Sydney, Sydney, NSW 2010, Australia.
5
The University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia. Electronic address: k.khosrotehrani@uq.edu.au.

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.

KEYWORDS:

aorta; endothelial cell; endovascular progenitor; hierarchy; single-cell RNA sequencing; transcriptome

PMID:
31141696
DOI:
10.1016/j.celrep.2019.04.102
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