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
Affiliations
Alessandro Arduini
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA
Stephen J. Fleming
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Data Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Ling Xiao
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA
Amelia W. Hall
Gene Regulation Observatory, The Broad Institute, Cambridge, MA 02142, USA
Amer-Denis Akkad
Precision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USA
Mark D. Chaffin
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA
Kayla J. Bendinelli
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA
Nathan R. Tucker
SUNY Upstate Medical University, Syracuse, NY 13210, USA
Irinna Papangeli
Precision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USA
Helene Mantineo
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA
Patricio Flores-Bringas
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA
Mehrtash Babadi
Data Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Christian M. Stegmann
Precision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USA
Guillermo García-Cardeña
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02215, USA
Mark E. Lindsay
Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA
Carla Klattenhoff
Precision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USA
Patrick T. Ellinor
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; Corresponding author
Summary: 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.
