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Cells and gene expression programs in the adult human heart

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Item Type:Preprint
Title:Cells and gene expression programs in the adult human heart
Creators Name:Litviňuková, M. and Talavera-López, C. and Maatz, H. and Reichart, D. and Worth, C.L. and Lindberg, E.L. and Kanda, M. and Polanski, K. and Fasouli, E.S. and Samari, S. and Roberts, K. and Tuck, L. and Heinig, M. and DeLaughter, D.M. and McDonough, B. and Wakimoto, H. and Gorham, J.M. and Nadelmann, E.R. and Mahbubani, K.T. and Saeb-Parsy, K. and Patone, G. and Boyle, J.J. and Zhang, H. and Zhang, H. and Viveiros, A. and Oudit, G.Y. and Bayraktar, O. and Seidman, J.G. and Seidman, C. and Noseda, M. and Hübner, N. and Teichmann, S.A.
Abstract:Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2020.04.03.024075
Date:10 April 2020
Official Publication:https://doi.org/10.1101/2020.04.03.024075

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