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      Cells of the adult human heart

      research-article
      1 , 2 , 1 , 3 , 2 , 4 , 5 , 2 , 2 , 2 , 6 , 1 , 7 , 8 , 9 , 4 , 1 , 1 , 1 , 4 , 4 , 11 , 16 , 4 , 4 , 9 , 12 , 12 , 2 , 9 , 1 , 13 , 14 , 15 , 14 , 15 , 14 , 15 , 1 , 4 , , 4 , 11 , 16 , , 9 , 17 , , 2 , 10 , 18 , 19 , , 1 , 20 ,
      Nature
      Nature Publishing Group UK
      Gene expression, Genetics research

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          Abstract

          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.

          Abstract

          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.

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          Most cited references95

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          Fiji: an open-source platform for biological-image analysis.

          Fiji is a distribution of the popular open-source software ImageJ focused on biological-image analysis. Fiji uses modern software engineering practices to combine powerful software libraries with a broad range of scripting languages to enable rapid prototyping of image-processing algorithms. Fiji facilitates the transformation of new algorithms into ImageJ plugins that can be shared with end users through an integrated update system. We propose Fiji as a platform for productive collaboration between computer science and biology research communities.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

              Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.
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                Author and article information

                Contributors
                seidman@genetics.med.harvard.edu
                cseidman@genetics.med.harvard.edu
                m.noseda@imperial.ac.uk
                nhuebner@mdc-berlin.de
                st9@sanger.ac.uk
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                24 September 2020
                : 1-7
                Affiliations
                [1 ]Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK
                [2 ]ISNI 0000 0001 1014 0849, GRID grid.419491.0, Cardiovascular and Metabolic Sciences, , Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), ; Berlin, Germany
                [3 ]EMBL - EBI, Wellcome Genome Campus, Hinxton, UK
                [4 ]ISNI 000000041936754X, GRID grid.38142.3c, Department of Genetics, , Harvard Medical School, ; Boston, MA USA
                [5 ]ISNI 0000 0001 2287 2617, GRID grid.9026.d, Department of Cardiology, , University Heart & Vascular Center, University of Hamburg, ; Hamburg, Germany
                [6 ]ISNI 0000 0001 0691 0855, GRID grid.263171.0, Department of Rheumatology and Clinical Immunology, , Sapporo Medical University, ; Sapporo, Japan
                [7 ]ISNI 0000 0004 0483 2525, GRID grid.4567.0, Institute of Computational Biology (ICB), HMGU, ; Neuherberg, Germany
                [8 ]ISNI 0000000123222966, GRID grid.6936.a, Department of Informatics, , Technische Universitaet Muenchen (TUM), ; Munich, Germany
                [9 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, National Heart and Lung Institute, , Imperial College London, ; London, UK
                [10 ]ISNI 0000 0004 5937 5237, GRID grid.452396.f, DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, ; Berlin, Germany
                [11 ]ISNI 0000 0004 0378 8294, GRID grid.62560.37, Cardiovascular Division, Brigham and Women’s Hospital, ; Boston, MA USA
                [12 ]ISNI 0000000121885934, GRID grid.5335.0, Department of Surgery, , University of Cambridge, NIHR Cambridge Biomedical Centre, Cambridge Biorepository for Translational Medicine, ; Cambridge, UK
                [13 ]ISNI 0000 0001 2360 039X, GRID grid.12981.33, Department of Histology and Embryology of Zhongshan School of Medicine, , Sun-Yat Sen University, ; Guangzhou, China
                [14 ]GRID grid.17089.37, Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, , University of Alberta, ; Edmonton, Alberta Canada
                [15 ]GRID grid.17089.37, Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, , University of Alberta, ; Edmonton, Alberta Canada
                [16 ]ISNI 0000 0001 2167 1581, GRID grid.413575.1, Howard Hughes Medical Institute, ; Chevy Chase, MD USA
                [17 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, British Heart Foundation Centre of Regenerative Medicine, British Heart Foundation Centre of Research Excellence, , Imperial College London, ; London, UK
                [18 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Charité-Universitätsmedizin, ; Berlin, Germany
                [19 ]GRID grid.484013.a, Berlin Institute of Health (BIH), ; Berlin, Germany
                [20 ]ISNI 0000000121885934, GRID grid.5335.0, Deptartment of Physics, Cavendish Laboratory, , University of Cambridge, ; Cambridge, UK
                Author information
                http://orcid.org/0000-0002-1796-9606
                http://orcid.org/0000-0003-3468-3586
                http://orcid.org/0000-0002-2586-9576
                http://orcid.org/0000-0002-5612-1720
                http://orcid.org/0000-0002-0186-4439
                http://orcid.org/0000-0001-6155-0821
                http://orcid.org/0000-0003-0225-6424
                http://orcid.org/0000-0002-1327-2334
                http://orcid.org/0000-0002-0633-3696
                http://orcid.org/0000-0002-7242-0341
                http://orcid.org/0000-0002-4337-3320
                http://orcid.org/0000-0001-6055-277X
                http://orcid.org/0000-0001-6380-1209
                http://orcid.org/0000-0002-9553-5029
                http://orcid.org/0000-0002-1218-6223
                http://orcid.org/0000-0002-6294-6366
                Article
                2797
                10.1038/s41586-020-2797-4
                7681775
                32971526
                4b757b9c-327b-44bd-b2c9-c68bbddc1d21
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 February 2020
                : 18 September 2020
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                gene expression,genetics research
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                gene expression, genetics research

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