Single-Nucleus RNA-Seq of Human and Rat Cardiomyocytes Identifies Shared and Distinct Regulators and Features of Aging and Disease
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Le résumé fourni par la source
Age is the greatest risk factor for cardiovascular diseases, including heart failure (HF), which is a leading cause of morbidity and mortality. While left ventricular fibrosis, hypertrophy and decreased contractility are associated with cardiac aging, age is not sufficient for HF development. Despite diminished cardiomyocyte (CM) function being central to cardiac pathology, whether factors predisposing the aged CM to disease are the same or distinct from those underlying disease are not determined. To address this, we integrated our own and published single-nucleus RNA-Seq data of different cardiomyopathies and from young and old human samples and probed for unique and overlapping features. To test the utility of rodents for modelling human aging and disease, we compared human data with data from deeply phenotyped relevant rat models. We identified diverse CM substates, which were significantly altered in proportion with pathology in human and in both pathology and age in rat. In human and rat, CM exhibited substantial transcriptomic changes with age and pathology. In addition to established hallmarks of cardiomyopathy and aging, we detected etiology/age-specific differentially expressed genes/pathways and identified candidate nodal regulators underlying these changes. In human and rat, CM exhibited greater cellular and transcriptional heterogeneity in pathology and age. While rats showed substantial differences to humans, overlapping features, including increased CM heterogeneity and altered expression of genes related to epigenetic, fibrotic and hypertrophic remodelling, were also detected. Although some pathways, differentially expressed genes and trajectories are shared between age and pathology, unique aspects support age and pathology as distinct entities.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Single-Nucleus RNA-Seq of Human and Rat Cardiomyocytes Identifies Shared and Distinct Regulators and Features of Aging and Disease
- Date Crossref
- 01/01/2026
- Éditeur
- Aging and Disease
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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KU Leuven pays non établi dans la noticeUniversité ou école supérieure
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Oslo University Hospital Institute for Experimental Medical Research pays non établi dans la noticeÉtablissement de santé
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University of Oslo pays non établi dans la noticeUniversité ou école supérieure
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Institutt for Eksperimentell Medisinsk Forskning pays non établi dans la noticeUniversité ou école supérieure
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Cardiovascular Institute of the South pays non établi dans la noticeInstitution
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University of Pennsylvania pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Experimental Cardiology pays non établi dans la noticeStructure de recherche
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University Hospitals Leuven Department of Cardiac Surgery pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Cardiac Surgery pays non établi dans la noticeStructure de recherche
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Perelman School of Medicine Cardiovascular Institute pays non établi dans la noticeUniversité ou école supérieure
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Leuven Institute for Single Cell Omics (LISCO) pays non établi dans la noticeStructure de recherche
KU Leuven, Institute for Experimental Medical Research — Oslo University Hospital et University of Oslo, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.