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10 reviewsCardiovascular disease is the leading cause of death globally. An advanced Introductionunderstanding of cardiovascular disease mechanisms is required to Successes and challenges improve therapeutic strategies and patient risk stratifcation. Statein experimental designof-the-art, large-scale, single-cell and single-nucleus transcriptomics Overview of the computational workflowfacilitate the exploration of the cardiac cellular landscape at an unprecedented level, beyond its descriptive features, and can further Cardiomyocyte profiling in health and diseaseour understanding of the mechanisms of disease and guide functional Fibroblasts in health and studies. In this Review, we provide an overview of the technical diseasechallenges in the experimental design of single-cell and single-nucleus Vascular cell signatures transcriptomics studies, as well as a discussion of the type of inferences in health and diseasethat can be made from the data derived from these studies. Furthermore, Dynamic adaptations we describe novel fndings derived from transcriptomics studies for each of immune cellsmajor cardiac cell type in both health and disease, and from development Functionally important rare to adulthood. This Review also provides a guide to interpreting the cell typesexhaustive list of newly identifed cardiac cell types and states, and Cellular networkshighlights the consensus and discordances in annotation, indicating Future directions for omics an urgent need for standardization. We describe advanced applications approachessuch as integration of single-cell data with spatial transcriptomics to Conclusionsmap genes and cells on tissue and defne 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
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