Single-cell dissection of live human hearts in ischemic heart disease and heart failure reveals cell-type-specific driver genes and pathways

Linna-Kuosmanen, S.; Schmauch, E.; Galani, K.; Boix, C. A.; Hou, L.; Örd, T.; Toropainen, A.; Stolze, L. K.; Meibalan, E.; Mantero, J. C.; Renfro, A.; Ojanen, J.; Agudelo, L. Z.; Hollmen, M.; Jalkanen, J.; Gunn, J.; Tavi, P.; Romanoski, C. E.; MacRae, C. A.; Kaikkonen, M. U.; Garcia-Cardena, G.; Kiviniemi, T.; Kellis, M.

doi:10.1101/2021.06.23.449672

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bioRxiv · 10.1101/2021.06.23.449672

Single-cell dissection of live human hearts in ischemic heart disease and heart failure reveals cell-type-specific driver genes and pathways

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Abstract

Ischemic heart disease is globally the leading cause of death. It plays a central role in the electrical and structural remodeling of the right atrium, predisposing to arrhythmias, heart failure, and sudden death. Here, we provide the first dissection of the gene expression changes in the live right atrial tissue, using single-nuclei RNA-seq and spatial transcriptomics. We investigate matched samples of the tissue and pericardial fluid and reveal substantial differences in disease- associated gene expression in all cell types, leading to inflammatory microvascular dysfunction and changes in the tissue composition. Our study demonstrates the importance of creating high- resolution cellular maps and partitioning disease signals beyond epicardial coronary arteries and ischemic left ventricle to identify candidate mechanisms leading to more severe types of human cardiovascular disease. One-Sentence SummarySingle-cell dissection of ex vivo heart biopsies and pericardial fluid in ischemic heart disease and heart failure

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Linna-Kuosmanen, S., Schmauch, E., Galani, K., Boix, C. A., Hou, L., Örd, T., Toropainen, A., Stolze, L. K., Meibalan, E., Mantero, J. C., Renfro, A., Ojanen, J., Agudelo, L. Z., Hollmen, M., Jalkanen, J., Gunn, J., Tavi, P., Romanoski, C. E., MacRae, C. A., Kaikkonen, M. U., Garcia-Cardena, G., Kiviniemi, T., Kellis, M.. 2021-06-24. Single-cell dissection of live human hearts in ischemic heart disease and heart failure reveals cell-type-specific driver genes and pathways. https://doi.org/10.1101/2021.06.23.449672

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