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Spatial multi-omic map of human myocardial infarction

View ORCID ProfileChristoph Kuppe, View ORCID ProfileRicardo O. Ramirez Flores, View ORCID ProfileZhijian Li, Monica Hannani, View ORCID ProfileJovan Tanevski, Maurice Halder, Mingbo Cheng, Susanne Ziegler, Xiaoting Zhang, Fabian Preisker, View ORCID ProfileNadine Kaesler, View ORCID ProfileYaoxian Xu, Remco M. Hoogenboezem, View ORCID ProfileEric M.J. Bindels, View ORCID ProfileRebekka K. Schneider, View ORCID ProfileHendrik Milting, View ORCID ProfileIvan G. Costa, View ORCID ProfileJulio Saez-Rodriguez, View ORCID ProfileRafael Kramann
doi: https://doi.org/10.1101/2020.12.08.411686
Christoph Kuppe
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
2Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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Ricardo O. Ramirez Flores
3Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
4Heidelberg University, Faculty of Biosciences, Heidelberg, Germany
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Zhijian Li
5Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany
6Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Monica Hannani
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
3Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
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Jovan Tanevski
3Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
7Department of Knowledge Technologies, Jožef Stefan Institute, Ljubljana, Slovenia
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Maurice Halder
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Mingbo Cheng
5Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany
6Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Susanne Ziegler
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Xiaoting Zhang
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Fabian Preisker
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Nadine Kaesler
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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  • ORCID record for Nadine Kaesler
Yaoxian Xu
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
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Remco M. Hoogenboezem
8Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Eric M.J. Bindels
8Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Rebekka K. Schneider
9Department of Cell Biology, RWTH Aachen University
10Department of Developmental Biology, Erasmus Medical Center, Rotterdam, The Netherlands
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Hendrik Milting
11Erich & 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
5Institute for Computational Genomics, RWTH Aachen University Hospital, Aachen, Germany
6Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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Julio Saez-Rodriguez
3Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany
6Joint Research Center for Computational Biomedicine, RWTH Aachen University Hospital, Aachen, Germany
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  • For correspondence: rkramann@gmx.net julio.saez@uni-heidelberg.de
Rafael Kramann
1Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen, Germany
2Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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  • For correspondence: rkramann@gmx.net julio.saez@uni-heidelberg.de
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Abstract

Myocardial infarction is a leading cause of mortality. While advances in the acute treatment have been made, the late-stage mortality is still high, driven by an incomplete understanding of cardiac remodeling processes1,2. Here we used single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of different physiological zones and timepoints of human myocardial infarction and human control myocardium to generate an integrative high-resolution map of cardiac remodeling. This approach allowed us to increase spatial resolution of cell-type composition and provide spatially resolved insights into the cardiac transcriptome and epigenome with identification of distinct cellular zones of injury, repair and remodeling. We here identified and validated mechanisms of fibroblast to myofibroblast differentiation that drive cardiac fibrosis. Our study provides an integrative molecular map of human myocardial infarction and represents a reference to advance mechanistic and therapeutic studies of cardiac disease.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† Co-first/senior authors

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 10, 2020.
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Spatial multi-omic map of human myocardial infarction
Christoph Kuppe, Ricardo O. Ramirez Flores, Zhijian Li, Monica Hannani, Jovan Tanevski, Maurice Halder, Mingbo Cheng, Susanne Ziegler, Xiaoting Zhang, Fabian Preisker, Nadine Kaesler, Yaoxian Xu, Remco M. Hoogenboezem, Eric M.J. Bindels, Rebekka K. Schneider, Hendrik Milting, Ivan G. Costa, Julio Saez-Rodriguez, Rafael Kramann
bioRxiv 2020.12.08.411686; doi: https://doi.org/10.1101/2020.12.08.411686
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Spatial multi-omic map of human myocardial infarction
Christoph Kuppe, Ricardo O. Ramirez Flores, Zhijian Li, Monica Hannani, Jovan Tanevski, Maurice Halder, Mingbo Cheng, Susanne Ziegler, Xiaoting Zhang, Fabian Preisker, Nadine Kaesler, Yaoxian Xu, Remco M. Hoogenboezem, Eric M.J. Bindels, Rebekka K. Schneider, Hendrik Milting, Ivan G. Costa, Julio Saez-Rodriguez, Rafael Kramann
bioRxiv 2020.12.08.411686; doi: https://doi.org/10.1101/2020.12.08.411686

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