Oral Presentation ANZSCDB National Scientific Meeting 2019

Single cell profiling of aortic endothelium identifies hierarchy from endovascular progenitors to differentiated cells (66571)

Jatin Patel 1 , Samuel W Lukowski 2 , Seenling Sim 1 , Ho Yi Wong 1 , Joshua Tay 3 , Ingrid Winkler 3 , Kiarash Khosrotehrani 1
  1. Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia
  2. Institute of Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  3. Mater Research Institute, Woolloongabba, QLD, Australia

Background: The circulatory system throughout an organism are lined by specialized endothelial cells that form the lumen of the vasculature tube. It is becoming apparent that within each organ bed the endothelial compartment is heterogeneous. However, the cellular and molecular profiles that govern the endothelial heterogeneity of the circulatory system are yet to be elucidated. Methods and Results: Using the vascular lineage tracing mouse model Cdh5CreER/Rosa-YFP, an unbiased data-driven approach to study the endothelial compartment of aorta via droplet-based single cell RNA sequencing was conducted. We show that two main transcriptionally distinct endothelial populations co-exist. These two populations recapitulate a hierarchy of endovascular progenitor (EVP) to differentiated endothelial cells. Using two independent trajectory analysis methods, we confirmed that they represent transitioning cells rather than discrete cell types. Gene co-expression analysis revealed crucial regulatory networks underlying each population, including significant metabolic and quiescent cell-cycle gene networks in the EVP. Using mitochondrial metabolism assays, we confirmed the EVP to have higher metabolic activity than more differentiated endothelial cells. The identities of these populations at single cell level strongly correlated to bulk RNA-seq data of sorted endothelial populations from normal and tumor-derived vasculature. Conclusion: In summary, these findings strongly support the existence of an endothelial hierarchy from EVP to differentiated endothelial cells that reside within the vascular wall of the adult aorta.