Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require deeper understanding of the healthy heart’s molecular processes. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using state-of-the-art analyses of large-scale single-cell and nuclei transcriptomes, we characterise six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes, and fibroblasts, revealing distinct atrial and ventricular subsets with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment we identify cardiac resident macrophages with inflammatory and protective transcriptional signatures. Further, inference of cell-cell interactions highlight different macrophage-fibroblast-cardiomyocyte networks between atria and ventricles that are distinct from skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a healthy reference for future studies.
FACS gating strategy for removal of cell debris and purification of nuclei. a. Size gating to remove doublets and aggregates was applied (SSC-A, FSC-A, SSC-W, SSC-H, FSC-H, FSC-W), followed by sorts for Hoechst-positive nuclei (purple population). Used for all nuclei processed in North America b. Example of negative control (no NucBlue Live ReadyProbes Reagent applied, ThermoFisher) with the same parameters as a. c. Gating strategy used for all nuclei processed in the United Kingdom. The Hoechst-positive nuclei were selected in P1. Further gating for size was applied (P2, P3) to remove doublets and aggregates. d. Example of a negative control with the same parameters as c.
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Litviňuková, M., Talavera-López, C., Maatz, H. et al. Cells of the adult human heart. Nature (2020). https://doi.org/10.1038/s41586-020-2797-4
Nature Reviews Cardiology (2020)