January 2025, Cell Reports: Transcriptional profile of the rat cardiovascular system at single-cell resolution

One of our first single cell studies of the microfluidic era finally out in print. The rat presented several unique challenges for our analysis, most notably a surprisingly poor annotation of the rat genome. End result: A rather comprehensive atlas of an important pre-clinical model with some excellent anatomical resolution.

Abstract from DOI: 10.1016/j.celrep.2024.115091

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.