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  • Review Article
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Single-cell transcriptomics for the assessment of cardiac disease

Nature Reviews Cardiology volume 20, pages 289–308 (2023)Cite this article

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Abstract

Cardiovascular disease is the leading cause of death globally. An advanced understanding of cardiovascular disease mechanisms is required to improve therapeutic strategies and patient risk stratification. State-of-the-art, large-scale, single-cell and single-nucleus transcriptomics facilitate the exploration of the cardiac cellular landscape at an unprecedented level, beyond its descriptive features, and can further our understanding of the mechanisms of disease and guide functional studies. In this Review, we provide an overview of the technical challenges in the experimental design of single-cell and single-nucleus transcriptomics studies, as well as a discussion of the type of inferences that can be made from the data derived from these studies. Furthermore, we describe novel findings derived from transcriptomics studies for each major cardiac cell type in both health and disease, and from development to adulthood. This Review also provides a guide to interpreting the exhaustive list of newly identified cardiac cell types and states, and highlights the consensus and discordances in annotation, indicating an urgent need for standardization. We describe advanced applications such as integration of single-cell data with spatial transcriptomics to map genes and cells on tissue and define cellular microenvironments that regulate homeostasis and disease progression. Finally, we discuss current and future translational and clinical implications of novel transcriptomics approaches, and provide an outlook of how these technologies will change the way we diagnose and treat heart disease.

Key points

  • A good experimental design requires a matching of the protocol workflow to the cells of interest and scientific goals.

  • The generation of reference heart cell atlases and standardized annotations is necessary for cross-study comparisons and accurate data interpretation.

  • Emerging disease gene signatures reveal cell-state-specific changes, which will facilitate the generation of novel putative biomarkers and therapeutic targets.

  • The definition of cellular microenvironments requires deconvolution with spatial and multi-omics approaches.

  • The density of information from these novel omics approaches will contribute to the design of computational models to predict disease, stratify patients and facilitate drug discovery.

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Fig. 1: Workflow for single-cell and single-nucleus transcriptomics.
Fig. 2: Computational analysis workflow.
Fig. 3: Single-cell and single-nucleus analysis revealed previously unknown complexities within fibroblasts.
Fig. 4: Species-specific expression of gene markers in endothelial cells of healthy and diseased hearts.
Fig. 5: Integrating scRNA-seq and snRNA-seq data with spatial transcriptomics analysis to define cellular microenvironments and their dynamic intercellular signalling networks.

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Acknowledgements

S.A.T. is supported by a Wellcome Sanger Institute grant (WT206194) and the Wellcome Science Strategic Support for a Pilot for the Human Cell Atlas (WT211276/Z/18/Z). N.H. is the recipient of an ERC Advanced Grant under the European Union Horizon 2020 Research and Innovation Program (AdG788970) and the Federal Ministry of Education and Research of Germany in the framework of CaRNAtion (031L0075A). M.D.S. received funding from the British Heart Foundation (CH/08/002/292257, RE/13/4/30184, RG/15/1/31165) and the European Research Council (233158). R.P.H. is supported by a National Health and Medical Research Council of Australia Investigator Grant (2021/GNT20087443) and Ideas Grant (2020/GNT2000615). M.N. received funding from the British Heart Foundation (PG/16/47/32156). S.A.T., N.H. and M.N. have received funding from a BHF/DZHK grant (SP/19/1/34461) and from the Chan Zuckerberg Initiative (2021-237882 and 2019-202666). The authors thank E. Adami (Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany) for her help with Table 1.

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Authors and Affiliations

  1. National Heart and Lung Institute, Imperial College London, London, UK

    Antonio M. A. Miranda, Michael D. Schneider & Michela Noseda

  2. Victor Chang Cardiac Research Institute, Sydney, NSW, Australia

    Vaibhao Janbandhu & Richard P. Harvey

  3. School of Clinical Medicine, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia

    Vaibhao Janbandhu & Richard P. Harvey

  4. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

    Henrike Maatz & Norbert Hübner

  5. Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK

    Kazumasa Kanemaru, James Cranley & Sarah A. Teichmann

  6. Deptartment of Physics, Cavendish Laboratory, University of Cambridge, Cambridge, UK

    Sarah A. Teichmann

  7. Charite-Universitätsmedizin Berlin, Berlin, Germany

    Norbert Hübner

  8. German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany

    Norbert Hübner

  9. School of Biotechnology and Biomolecular Sciences, UNSW Sydney, Sydney, NSW, Australia

    Richard P. Harvey

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A.M.A.M., V.J., H.M., K.K., J.C., M.D.S. R.P.H. and M.N. researched data for the article. and wrote the manuscript. A.M.A.M., V.J., H.M., K.K., S.A.T., N.H., M.D.S., R.P.H. and M.N. contributed to the discussion of content. All authors reviewed and edited the manuscript before submission.

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Competing interests

S.A.T. has consulted for or has been a member of scientific advisory boards at Biogen, ForeSite Labs, Genentech, GlaxoSmithKline, Qiagen and Roche, and is an equity holder of Transition Bio. All other authors declare no competing interests.

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Miranda, A.M.A., Janbandhu, V., Maatz, H. et al. Single-cell transcriptomics for the assessment of cardiac disease. Nat Rev Cardiol 20, 289–308 (2023). https://doi.org/10.1038/s41569-022-00805-7

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