Journal Article

Spatial multi-omic map of human myocardial infarction

Wünnemann, Florian, Ramirez Flores, Ricardo O., Halder, Maurice, Schurgers, Leon, Kassner, Astrid, Hayat, Sikander, Menzel, Sylvia, Cheng, Mingbo, Veltrop, Rogier J. A., Ziegler, Susanne, Xu, Yaoxian, Saez-Rodriguez, Julio, Kramann, Rafael, Schneider, Rebekka K., Tanevski, Jovan, Gummert, Jan, Li, Zhijian, Lavine, Kory, Vink, Aryan, Hoogenboezem, Remco M., Kaesler, Nadine, Bindels, Eric M. J., Peisker, Fabian, Schumacher, David, Van Laake, Linda W., Kuppe, Christoph, Boor, Peter, Klingel, Karin, Hoeft, Konrad, Saritas, Turgay, Amrute, Junedh, Sattler, Susanne, Levinson, Rebecca T., Hannani, Monica T., Schapiro, Denis, Milting, Hendrik, Costa, Ivan G., Nagai, James S., Zhang, Xiaoting, Liao, Xian, Schäfer, Gideon, Morshuis, Michiel

2022

Overview

Myocardial infarction is a leading cause of death worldwide 1 . Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality 2 . 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/105 / 14 / 38/39 / 631/114/2401 / 631/337/2019 / 64 / 64/60 / 692/699/75/2/1674 / Apoptosis / Atrial Remodeling - genetics / Cardiomyocytes / Cardiovascular disease / Case-Control Studies / Chromatin / Chromatin - genetics / Chromatin Assembly and Disassembly / Coronary artery disease / Data integration / Datasets / Epigenome / Fibroblasts / Gene expression / Gene Expression Profiling / Genomics / Heart attacks / Heart diseases / Homeostasis / Humanities and Social Sciences / Humans / Ischemia / Modal data / Mortality / multidisciplinary / Myocardial infarction / Myocardial Infarction - genetics / Myocardial Infarction - pathology / Myocardium / Myocardium - metabolism / Myocardium - pathology / Myocytes, Cardiac - metabolism / Myocytes, Cardiac - pathology / Science / Science (multidisciplinary) / Sensory integration / Single-Cell Analysis / Time Factors / Transcriptomes / Transcriptomics / Ventricular Remodeling - genetics