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

Alessandro Arduini; Stephen J Fleming; Ling Xiao; Amelia W Hall; Amer-Denis Akkad; Mark D Chaffin; Kayla J Bendinelli; Nathan R Tucker; Irinna Papangeli; Helene Mantineo; Patricio Flores-Bringas; Mehrtash Babadi; Christian M Stegmann; Guillermo García-Cardeña; Mark E Lindsay; Carla Klattenhoff; Patrick T Ellinor

doi:10.1016/j.celrep.2024.115091

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

Cell Rep. 2024 Dec 21;44(1):115091. doi: 10.1016/j.celrep.2024.115091. Online ahead of print.

Authors

Alessandro Arduini¹, Stephen J Fleming², Ling Xiao³, Amelia W Hall⁴, Amer-Denis Akkad⁵, Mark D Chaffin¹, Kayla J Bendinelli¹, Nathan R Tucker⁶, Irinna Papangeli⁵, Helene Mantineo³, Patricio Flores-Bringas¹, Mehrtash Babadi⁷, Christian M Stegmann⁵, Guillermo García-Cardeña⁸, Mark E Lindsay³, Carla Klattenhoff⁵, Patrick T Ellinor⁹

Affiliations

¹ Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA.
² Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Data Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴ Gene Regulation Observatory, The Broad Institute, Cambridge, MA 02142, USA.
⁵ Precision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USA.
⁶ SUNY Upstate Medical University, Syracuse, NY 13210, USA.
⁷ Data Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
⁹ Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiology Division, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: ellinor@mgh.harvard.edu.

PMID: 39709602
DOI: 10.1016/j.celrep.2024.115091

Abstract

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.

Keywords: CP: Developmental biology; atrioventricular node; cardiovascular disease; cardiovascular system; cell-cell communication; genetics; heart; pulmonary vein; rat; single-nuclei RNA sequencing; single-nucleus RNA sequencing; sinoatrial node.