PMID- 35948637 OWN - NLM STAT- MEDLINE VI - 608 IP - 7924 TI - Spatial multi-omic map of human myocardial infarction. PG - 766-777 CI - © 2022. The Author(s), under exclusive licence to Springer Nature Limited. LA - eng PT - Journal Article PL - England TA - Nature JT - Nature JID - 0410462 IS - 1476-4687 (Electronic) LID - 10.1038/s41586-022-05060-x [doi] FAU - Kuppe, Christoph AU - Kuppe C AUID- ORCID: http://orcid.org/0000-0003-4597-9833 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Ramirez Flores, Ricardo O AU - Ramirez Flores RO AUID- ORCID: http://orcid.org/0000-0003-0087-371X AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. AD - Informatics for Life, Heidelberg, Germany. FAU - Li, Zhijian AU - Li Z AUID- ORCID: http://orcid.org/0000-0002-1523-1333 AD - Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany. FAU - Hayat, Sikander AU - Hayat S AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Levinson, Rebecca T AU - Levinson RT AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. AD - Informatics for Life, Heidelberg, Germany. AD - Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg, Germany. FAU - Liao, Xian AU - Liao X AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Hannani, Monica T AU - Hannani MT AUID- ORCID: http://orcid.org/0000-0002-4123-6832 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. FAU - Tanevski, Jovan AU - Tanevski J AUID- ORCID: http://orcid.org/0000-0001-7177-1003 AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. AD - Department of Knowledge Technologies, Jožef Stefan Institute, Ljubljana, Slovenia. FAU - Wünnemann, Florian AU - Wünnemann F AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. FAU - Nagai, James S AU - Nagai JS AD - Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany. FAU - Halder, Maurice AU - Halder M AUID- ORCID: http://orcid.org/0000-0003-2386-9684 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Schumacher, David AU - Schumacher D AUID- ORCID: http://orcid.org/0000-0002-2308-6543 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Menzel, Sylvia AU - Menzel S AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Schäfer, Gideon AU - Schäfer G AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Hoeft, Konrad AU - Hoeft K AUID- ORCID: http://orcid.org/0000-0002-0265-0061 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Cheng, Mingbo AU - Cheng M AD - Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany. FAU - Ziegler, Susanne AU - Ziegler S AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Zhang, Xiaoting AU - Zhang X AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Peisker, Fabian AU - Peisker F AUID- ORCID: http://orcid.org/0000-0003-0123-8179 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Kaesler, Nadine AU - Kaesler N AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Saritas, Turgay AU - Saritas T AUID- ORCID: http://orcid.org/0000-0002-6691-9218 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Xu, Yaoxian AU - Xu Y AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. FAU - Kassner, Astrid AU - Kassner A AD - Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany. FAU - Gummert, Jan AU - Gummert J AD - Heart and Diabetes Center, North Rhine-Westphalia, Bad Oeynhausen, Germany. FAU - Morshuis, Michiel AU - Morshuis M AD - Heart and Diabetes Center, North Rhine-Westphalia, Bad Oeynhausen, Germany. FAU - Amrute, Junedh AU - Amrute J AUID- ORCID: http://orcid.org/0000-0002-6851-0168 AD - Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. FAU - Veltrop, Rogier J A AU - Veltrop RJA AUID- ORCID: http://orcid.org/0000-0002-1386-820X AD - Institute for Molecular Cardiovascular Research IMCAR, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. FAU - Boor, Peter AU - Boor P AUID- ORCID: http://orcid.org/0000-0001-9921-4284 AD - Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Department of Pathology, RWTH Aachen University, Aachen, Germany. FAU - Klingel, Karin AU - Klingel K AD - Cardiopathology, Institute for Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany. FAU - Van Laake, Linda W AU - Van Laake LW AD - Department of Cardiology, Regenerative Medicine Center and Circulatory Health Lab, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Vink, Aryan AU - Vink A AUID- ORCID: http://orcid.org/0000-0002-9371-8788 AD - Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. FAU - Hoogenboezem, Remco M AU - Hoogenboezem RM AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. FAU - Bindels, Eric M J AU - Bindels EMJ AUID- ORCID: http://orcid.org/0000-0001-9502-669X AD - Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. FAU - Schurgers, Leon AU - Schurgers L AUID- ORCID: http://orcid.org/0000-0001-7867-6957 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. FAU - Sattler, Susanne AU - Sattler S AUID- ORCID: http://orcid.org/0000-0001-9932-4109 AD - National Heart and Lung Institute, Imperial College London, London, UK. FAU - Schapiro, Denis AU - Schapiro D AUID- ORCID: http://orcid.org/0000-0002-9391-5722 AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. AD - Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany. FAU - Schneider, Rebekka K AU - Schneider RK AD - Institute of Cell and Tumor Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Oncode Institute, Erasmus Medical Center, Rotterdam, The Netherlands. FAU - Lavine, Kory AU - Lavine K AUID- ORCID: http://orcid.org/0000-0003-1948-9945 AD - Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. FAU - Milting, Hendrik AU - Milting H AD - Erich and Hanna Klessmann Institute for Cardiovascular Research and Development, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center NRW, Bad Oeynhausen, Germany. FAU - Costa, Ivan G AU - Costa IG AUID- ORCID: http://orcid.org/0000-0003-2890-8697 AD - Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany. AD - Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany. FAU - Saez-Rodriguez, Julio AU - Saez-Rodriguez J AUID- ORCID: http://orcid.org/0000-0002-8552-8976 AD - Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant, Heidelberg, Germany. pub.saez@uni-heidelberg.de. AD - Informatics for Life, Heidelberg, Germany. pub.saez@uni-heidelberg.de. FAU - Kramann, Rafael AU - Kramann R AUID- ORCID: http://orcid.org/0000-0003-4048-6351 AD - Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Medical Faculty, Aachen, Germany. rkramann@gmx.net. AD - Division of Nephrology and Clinical Immunology, RWTH Aachen University, Medical Faculty, Aachen, Germany. rkramann@gmx.net. AD - Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, The Netherlands. rkramann@gmx.net. IS - 0028-0836 (Linking) RN - 0 (Chromatin) SB - IM MH - *Atrial Remodeling/genetics MH - Case-Control Studies MH - Chromatin/genetics MH - *Chromatin Assembly and Disassembly MH - Epigenome MH - *Gene Expression Profiling MH - Humans MH - *Myocardial Infarction/genetics/pathology MH - Myocardium/metabolism/pathology MH - Myocytes, Cardiac/metabolism/pathology MH - *Single-Cell Analysis MH - Time Factors MH - *Ventricular Remodeling/genetics PMC - PMC9364862 DCOM- 20220826 LR - 20230104 DP - 202208 DEP - 20220810 AB - 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.