Single cell RNA-seq of adult mouse heart endothelial transcriptomes following myocardial infarction

A better understanding of the pathways that regulate regeneration of the coronary vasculature is of fundamental importance for the advancement of strategies to treat patients with heart disease. By analyzing single cell transcriptome of resident cardiac endothelial cells (ECs) in adult mouse hearts under both healthy and myocardial infarction (MI) settings, we provide molecular definitions of murine cardiac endothelial heterogeneity and characterizations of pro-angiogenic resident ECs. Overall design: An EC-specific multispectral lineage-tracing mouse (Pdgfb-iCreERT2-R26R-Brainbow2.1) was used to demonstrate that structural integrity of adult cardiac endothelium following MI was maintained through clonal proliferation by resident ECs in the infarct border region, without significant contributions from bone marrow cells or endothelial-to-mesenchymal transition. Single cell RNA-seq was performed on FACS-sorted CD31+Confetti+Podoplanin- cell populations isolated from four healthy and four 7-day post-MI adult mouse hearts. Ten transcriptionally discrete heterogeneous EC states, as well as the pathways through which each endothelial state is likely to enhance neovasculogenesis and tissue regeneration following ischaemic injury were defined.