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 KaeslerTurgay Saritas, Yaoxian Xu, Astrid Kassner, Jan Gummert, Michiel Morshuis, Junedh Amrute, Rogier J.A. Veltrop, Peter Boor, Karin Klingel, Linda W. Van 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, Rafael Kramann

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

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.

Original languageEnglish
Pages (from-to)766-777
Number of pages12
JournalNature
Volume608
Issue number7924
DOIs
StatePublished - Aug 25 2022

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