Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2

Figures

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  Fig. 1. The landscape of the cellular composition of the heart from healthy and CVD patients at a single-cell resolution. A UMAP plot showing annotated cardiomyocyte types; B Distribution of each cell type of cardiomyocytes in different disease states; C Proportions of different cell types in the left ventricle (up) and right ventricle (down); D Violin plot generated from the comprehensive dataset showing the signature marker genes for each identified cell population; E Pie chart of the proportions of cardiomyocyte types in different disease states; F UMAP diagram of the proportions of cardiomyocyte types in different disease states

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  Fig. 2. Distribution of ACE2, ADAM17 and CTSL. A Violin plot and scatterplot of ACE2 expression in different cell types in DCM, ICM, hypertension and healthy myocardial tissue; B ACE2+ADAM17+, ACE2+CTSL+ and ACE2+-LMAN2+ cells in different states and cell types, where blue represents double-positive cells; C Correlation between ACE2+ADAM17+ and cell type in DCM, ICM, hypertension and healthy myocardial tissue; D Marker genes of different cell types and the expression of ACE2, ADAM17 and CTSL in different cell types; E Volcano plot of the differential analysis of ACE2+ADAM17+ cells relative to all others; F Violin plot and scatter plot of ACE2, ADAM17 and CTSL expression in different cardiomyocyte subtypes

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  Fig. 3. Correlations of ACE2, ADAM17 and CTSL with clinical characteristics. A Violin and scatter plots of ACE2, ADAM17 and CTSL expression in 32 cardiomyocyte subtypes; B Clinical information for all patients whose single-cell data are used; C, D Correlations of age, sex, and different cardiovascular comorbidities with gene expression of ACE2 (orange), ADAM17 (green), CTSL (cyan) and LMAN (purple) in 3 cardiomyocyte subtypes

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  Fig. 4. Cell type-specific expression of other proteases. A–C Heat map of ACE2-related genes in ICM, DCM, and pericyte subsets of healthy tissues; D Heat map of differential gene expression analysis between ACE2+ADAM17+ cells and other cardiomyocytes; E Correlation analysis between ACE2 and other gene expression in different cardiomyocyte types; F Violin plot of expression levels of ACE2, AGT, PCSK5, CTSL, CALM3 and ADAM17 genes; G Histogram of cell proportions expressing the ACE2, AGT, PCSK5, CTSL, CALM3 and ADAM17 genes; H Histogram of the proportions of double-positive cells

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  Fig. 5. Enrichment analysis of ACE2+ADAM17+ and ACE2+CTSL+ cells. A ACE2+ADAM17+ cell-related genes in different tissues; B ACE2+CTSL+ cells in different tissues with associated genes; C ACE2+ADAM17+ cell-related gene KEGG enrichment results; D ACE2+CTSL+ cell-related gene KEGG enrichment results; E Genes associated with ACE2+CTSL+ cells in different cardiomyocyte subtypes

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  Fig. 6. Subdivision of pericytes and expression of specific helicases. A Pericellular distribution after redimensionalization and clustering; B The proportion of pericyte subsets in different CVD states; C Heatmap of differential genes in pericytes relative to other cells; D The proportion of cells expressing differentially expressed helicases in different cell types

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  Fig. 7. Differences in cell‒cell communication between DCM, ICM, hypertension and healthy tissue. A–C DCM, ICM and hypertension compared with healthy tissue, the intensity and number of cell‒cell communication differences between different cell types, and the differences in the IFN-II signaling pathway and PAR signaling pathway