Spatial multi-omic map of human myocardial infarction
Nature, vol. 608, pp. 766–777
Abstract
Myocardial infarction is a leading cause of death worldwide1. Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality2. Here we generate an integrative high-resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from patients with myocardial infarction and controls. Multi-modal data integration enabled us to evaluate cardiac cell-type compositions at increased resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the identification of distinct tissue structures of injury, repair and remodelling. We identified and validated disease-specific cardiac cell states of major cell types and analysed them in their spatial context, evaluating their dependency on other cell types. Our data elucidate the molecular principles of human myocardial tissue organization, recapitulating a gradual cardiomyocyte and myeloid continuum following ischaemic injury. In sum, our study provides an integrative molecular map of human myocardial infarction, represents an essential reference for the field and paves the way for advanced mechanistic and therapeutic studies of cardiac disease. A time-resolved high-resolution map of human cardiac remodelling after myocardial infarction, integrating single-cell transcriptomic, chromatin accessibility and spatial transcriptomic data, provides a valuable resource for the field.
Authors 42
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Christoph Kuppe Aachen Division of Nephrology and Clinical Immunology Institute of Experimental Medicine and Systems Biology
Affiliation as printed
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Informatics for Life, Heidelberg, Germany
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany
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Zhijian Li Aachen Institute for Computational Genomics Joint Research Center for Computational Biomedicine
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany
Informatics for Life, Heidelberg, Germany
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Heidelberg University · University Hospital Heidelberg · RWTH Aachen University
Affiliation as printed
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Heidelberg University · University Hospital Heidelberg · Jožef Stefan Institute · Jožef Stefan International Postgraduate School
Affiliation as printed
Department of Knowledge Technologies, Jožef Stefan Institute, Ljubljana, Slovenia
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany
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Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany
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James Shiniti Nagai Aachen Institute for Computational Genomics Joint Research Center for Computational Biomedicine
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Mingbo Cheng Aachen Institute for Computational Genomics Joint Research Center for Computational Biomedicine
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Nadine Kaesler Aachen Division of Nephrology and Clinical Immunology Institute of Experimental Medicine and Systems Biology
Affiliation as printed
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Turgay Saritas Aachen Division of Nephrology and Clinical Immunology Institute of Experimental Medicine and Systems Biology
Affiliation as printed
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Heart and Diabetes Center North Rhine-Westphalia
Affiliation as printed
Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany
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Heart and Diabetes Center North Rhine-Westphalia
Affiliation as printed
Heart and Diabetes Center, North Rhine-Westphalia, Bad Oeynhausen, Germany
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Heart and Diabetes Center North Rhine-Westphalia
Affiliation as printed
Heart and Diabetes Center, North Rhine-Westphalia, Bad Oeynhausen, Germany
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Washington University in St. Louis
Affiliation as printed
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
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Maastricht University · RWTH Aachen University
Affiliation as printed
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Institute for Molecular Cardiovascular Research IMCAR, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
Department of Pathology, RWTH Aachen University, Aachen, Germany
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Universitätsklinikum Tübingen · University of Tübingen
Affiliation as printed
Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Cardiology, Regenerative Medicine Center and Circulatory Health Lab, University Medical Center Utrecht, Utrecht, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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Affiliation as printed
Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Affiliation as printed
Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Maastricht University · RWTH Aachen University
Affiliation as printed
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
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Affiliation as printed
National Heart and Lung Institute, Imperial College London, London, UK
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Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany
Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany
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Erasmus MC · RWTH Aachen University
Affiliation as printed
Institute of Cell and Tumor Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany
Oncode Institute, Erasmus Medical Center, Rotterdam, The Netherlands
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Washington University in St. Louis
Affiliation as printed
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
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Heart and Diabetes Center North Rhine-Westphalia
Affiliation as printed
Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany
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Ivan G. Costa Aachen Institute for Computational Genomics Joint Research Center for Computational Biomedicine
Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Julio Sáez-Rodríguez corresponding
Heidelberg University · University Hospital Heidelberg
Affiliation as printed
Informatics for Life, Heidelberg, Germany. pub.saez@uni-heidelberg.de
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. pub.saez@uni-heidelberg.de
Informatics for Life, Heidelberg, Germany
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Rafael Kramann corresponding Aachen Division of Nephrology and Clinical Immunology Institute of Experimental Medicine and Systems Biology
Erasmus MC · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands. rkramann@gmx.net
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany. rkramann@gmx.net
Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. rkramann@gmx.net
Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands
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