Journal
NATURE
Volume 588, Issue 7838, Pages 466-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-2797-4
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Funding
- British Heart Foundation (BHF) grant [PG/16/47/32156]
- BHF grant [FS/13/12/30037, PG/15/57/31580, PG/17/71/33242]
- BHF/DZHK grant [SP/19/1/34461]
- ERC Advanced Grant under the European Union Horizon 2020 Research and Innovation Program [AdG788970]
- Federal Ministry of Education and Research of Germany [031L0075A]
- Leducq Fondation [16CVD03]
- German Research Foundation (DFG)
- long-term Chinese Council Scholarship (CSC)
- Alexander von Humboldt Foundation
- EMBO long-term postdoctoral fellowship
- CIHR Canadian Institutes for Health Research
- AI Alberta Innovates
- Chan Zuckerberg Initiative [2019202666]
- Wellcome Sanger Institute [WT206194]
- Wellcome Science Strategic Support for a Pilot for the Human Cell Atlas [WT211276/Z/18/Z]
- NIH [2R01HL080494, 1UM1HL098166]
- Engineering Research Centers Program of the National Science Foundation [EEC-1647837]
- Howard Hughes Medical Institute
- Sarnoff Cardiovascular Research Foundation
- HSF Heart and Stroke Foundation
- HMS MicRoN Core
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Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease. Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells 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. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.
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