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.
Authors
- Amer-Denis Akkad (ORCID: https://orcid.org/0000-0001-6266-947X)
- Guillermo García‐Cardeña (ORCID: https://orcid.org/0000-0003-2663-3706)
- Christian M. Stegmann (ORCID: https://orcid.org/0000-0001-7573-8948)
- Stephen J. Fleming (ORCID: https://orcid.org/0000-0002-1885-4405)
- Kayla J. Bendinelli (ORCID: https://orcid.org/0000-0002-4072-9002)
- Patricio Flores-Bringas (ORCID: https://orcid.org/0009-0005-2611-7463)
- Irinna Papangeli
- Carla Klattenhoff
- Mark E. Lindsay (ORCID: https://orcid.org/0000-0001-6724-7938)
- Nathan R. Tucker (ORCID: https://orcid.org/0000-0002-5071-4218)
- Mark D. Chaffin (ORCID: https://orcid.org/0000-0002-1234-5562)
- Patrick T. Ellinor (ORCID: https://orcid.org/0000-0002-2067-0533)
- Amelia Weber Hall (ORCID: https://orcid.org/0000-0002-7915-0313)
- Alessandro Arduini (ORCID: https://orcid.org/0000-0002-0038-8741)
- Mehrtash Babadi (ORCID: https://orcid.org/0000-0003-1829-8397)
- Helene Mantineo
- Ling Xiao (ORCID: https://orcid.org/0000-0003-3025-467X)
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- SUNY Upstate Medical University (US)
- Massachusetts General Hospital (US)
- Precision for Medicine (United States) (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-21
- DOI
- https://doi.org/10.1016/j.celrep.2024.115091
- Citations
- 11
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- Foundation for the National Institutes of Health
- American Heart Association
- European Commission
- National Institutes of Health
- H2020 European Research Council