Spatial multi-omic map of human myocardial infarction

Christoph Kuppe, Ricardo O. Ramirez Flores, Zhijian Li, Sikander Hayat, Rebecca T. Levinson, Xian Liao, Monica T. Hannani, Jovan Tanevski, Florian Wünnemann, James S. Nagai, Maurice Halder, David Schumacher, Sylvia Menzel, Gideon Schäfer, Konrad Hoeft, Mingbo Cheng, Susanne Ziegler, Xiaoting Zhang, Fabian Peisker, Nadine Kaesler, Turgay Saritas, Yaoxian Xu, Astrid Kassner, Jan Gummert, Michiel Morshuis, Junedh Amrute, Rogier J. A. Veltrop, Peter Boor, Karin Klingel, Linda W. Laake, Aryan Vink, Remco M. Hoogenboezem, Eric M. J. Bindels, Leon Schurgers, Susanne Sattler, Denis Schapiro, Rebekka K. Schneider, Kory Lavine, Hendrik Milting, Ivan G. Costa, Julio Saez-Rodriguez () and Rafael Kramann ()
Additional contact information
Christoph Kuppe: RWTH Aachen University, Medical Faculty
Ricardo O. Ramirez Flores: Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant
Zhijian Li: RWTH Aachen University, Medical Faculty
Sikander Hayat: RWTH Aachen University, Medical Faculty
Rebecca T. Levinson: Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant
Xian Liao: RWTH Aachen University, Medical Faculty
Monica T. Hannani: RWTH Aachen University, Medical Faculty
Jovan Tanevski: Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant
Florian Wünnemann: Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant
James S. Nagai: RWTH Aachen University, Medical Faculty
Maurice Halder: RWTH Aachen University, Medical Faculty
David Schumacher: RWTH Aachen University, Medical Faculty
Sylvia Menzel: RWTH Aachen University, Medical Faculty
Gideon Schäfer: RWTH Aachen University, Medical Faculty
Konrad Hoeft: RWTH Aachen University, Medical Faculty
Mingbo Cheng: RWTH Aachen University, Medical Faculty
Susanne Ziegler: RWTH Aachen University, Medical Faculty
Xiaoting Zhang: RWTH Aachen University, Medical Faculty
Fabian Peisker: RWTH Aachen University, Medical Faculty
Nadine Kaesler: RWTH Aachen University, Medical Faculty
Turgay Saritas: RWTH Aachen University, Medical Faculty
Yaoxian Xu: RWTH Aachen University, Medical Faculty
Astrid Kassner: Heart and Diabetes Center NRW
Jan Gummert: North Rhine-Westphalia
Michiel Morshuis: North Rhine-Westphalia
Junedh Amrute: Washington University School of Medicine
Rogier J. A. Veltrop: RWTH Aachen University, Medical Faculty
Peter Boor: RWTH Aachen University, Medical Faculty
Karin Klingel: University Hospital Tübingen
Linda W. Laake: University Medical Center Utrecht
Aryan Vink: University Medical Center Utrecht, Utrecht University
Remco M. Hoogenboezem: Erasmus MC Cancer Institute
Eric M. J. Bindels: Erasmus MC Cancer Institute
Leon Schurgers: RWTH Aachen University, Medical Faculty
Susanne Sattler: Imperial College London
Denis Schapiro: Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant
Rebekka K. Schneider: RWTH Aachen University, Medical Faculty
Kory Lavine: Washington University School of Medicine
Hendrik Milting: Heart and Diabetes Center NRW
Ivan G. Costa: RWTH Aachen University, Medical Faculty
Julio Saez-Rodriguez: Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Bioquant
Rafael Kramann: RWTH Aachen University, Medical Faculty

Nature, 2022, vol. 608, issue 7924, 766-777

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-022-05060-x

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