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

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 t...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724014426
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author 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
author_facet 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
author_sort Alessandro Arduini
collection DOAJ
description 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.
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spelling doaj-art-0767ac83a4d74870a6d56da8ae01844d2025-08-20T02:40:24ZengElsevierCell Reports2211-12472025-01-0144111509110.1016/j.celrep.2024.115091Transcriptional profile of the rat cardiovascular system at single-cell resolutionAlessandro Arduini0Stephen J. Fleming1Ling Xiao2Amelia W. Hall3Amer-Denis Akkad4Mark D. Chaffin5Kayla J. Bendinelli6Nathan R. Tucker7Irinna Papangeli8Helene Mantineo9Patricio Flores-Bringas10Mehrtash Babadi11Christian M. Stegmann12Guillermo García-Cardeña13Mark E. Lindsay14Carla Klattenhoff15Patrick T. Ellinor16Precision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Data Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USAGene Regulation Observatory, The Broad Institute, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USASUNY Upstate Medical University, Syracuse, NY 13210, USAPrecision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USAData Sciences Platform, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02215, USAPrecision Cardiology Laboratory, The Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USAPrecision Cardiology Laboratory, Bayer US LLC, Cambridge, MA 02142, USAPrecision 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724014426CP: Developmental biology
spellingShingle 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
Transcriptional profile of the rat cardiovascular system at single-cell resolution
Cell Reports
CP: Developmental biology
title Transcriptional profile of the rat cardiovascular system at single-cell resolution
title_full Transcriptional profile of the rat cardiovascular system at single-cell resolution
title_fullStr Transcriptional profile of the rat cardiovascular system at single-cell resolution
title_full_unstemmed Transcriptional profile of the rat cardiovascular system at single-cell resolution
title_short Transcriptional profile of the rat cardiovascular system at single-cell resolution
title_sort transcriptional profile of the rat cardiovascular system at single cell resolution
topic CP: Developmental biology
url http://www.sciencedirect.com/science/article/pii/S2211124724014426
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