Transcriptional profile of the rat cardiovascular system at single-cell resolution

We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed single-nucleus RNA sequencing (snRNA-seq) in 78 samples in 10 distinct regions, including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type. Several cell subtypes were region specific, including a subtype of vascular smooth muscle cells enriched in the large vasculature. We observed tissue-enriched cellular communication networks, including heightened Nppa-Npr1/2/3 signaling in the sinoatrial node. The existence of tissue-restricted cell types suggests regional regulation of cardiovascular physiology. Our detailed transcriptional characterization of each cell type offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease. [Display omitted] •Cell subtypes are present at different proportions in different regions•Certain endothelial and smooth muscle subtypes are unique to the large vessels•Endothelial cells have discrete subtypes; fibroblasts have a gradient of variation•We identified rare cell types such as Schwann cells and pacemaker cardiomyocytes Arduini et al. use single-nucleus RNA-seq to characterize many anatomical regions in the healthy rat heart, including the sinoatrial and atrioventricular nodes, as well as the pulmonary arteries, veins, and aorta. Many aspects of this 500,000 cell dataset are explored, including the regional specificity of various cell types and subtypes.