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.
Subject(s)
Myocardium/cytology , Single-Cell Analysis , Transcriptome , Adipocytes/classification , Adipocytes/metabolism , Adult , Angiotensin-Converting Enzyme 2/analysis , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Epithelial Cells/classification , Epithelial Cells/metabolism , Epithelium , Female , Fibroblasts/classification , Fibroblasts/metabolism , Gene Expression Profiling , Genome-Wide Association Study , Heart Atria/anatomy & histology , Heart Atria/cytology , Heart Atria/innervation , Heart Ventricles/anatomy & histology , Heart Ventricles/cytology , Heart Ventricles/innervation , Homeostasis/immunology , Humans , Macrophages/immunology , Macrophages/metabolism , Male , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Myocytes, Cardiac/classification , Myocytes, Cardiac/metabolism , Neurons/classification , Neurons/metabolism , Pericytes/classification , Pericytes/metabolism , Receptors, Coronavirus/analysis , Receptors, Coronavirus/genetics , Receptors, Coronavirus/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Stromal Cells/classification , Stromal Cells/metabolismABSTRACT
PURPOSE OF REVIEW: SARS-CoV-2, the recently emerged coronavirus (CoV) that is responsible for the current global pandemic Covid-19, first appeared in late 2019 in Wuhan, China. Here, we summarise details of the SARS-CoV-2 genome to assist understanding of the emergence, evolution and diagnosis of this deadly new virus. RECENT FINDINGS: Based on high similarities in the genome sequences, the virus is thought to have arisen from SARS-like CoVs in bats but the lack of an intermediate species containing a CoV with even greater similarity has so far eluded discovery. The critical determinant of the SARS-CoV-2 genome is the spike (S) gene encoding the viral structural protein that interacts with the host cell entry receptor ACE2. The S protein is sufficiently adapted to bind human ACE2 much more readily than SARS-CoV, the most closely related human CoV. SUMMARY: Although the SARS-CoV-2 genome is undergoing subtle evolution in humans through mutation that may enhance transmission, there is limited evidence for attenuation that might weaken the virus. It is also still unclear as to the events that led to the virus' emergence from bats. Importantly, current diagnosis requires specific recognition and amplification of the SARS-CoV-2 RNA genome by qPCR, despite these ongoing viral genome changes. Alternative diagnostic procedures relying on immunoassay are becoming more prevalent.