Fig. 4: Dysregulation of angiogenesis pathways due to SARS-CoV-2 infection.

a,b, GO analysis of upregulated genes from snRNA-seq in villous fibroblast cluster 1 (V.FB1; a) and villous vascular endothelial (V.Endo1; b) cells. The size and colour of the bubble represent the number of upregulated genes and the ratio to total genes under each GO term, respectively. P values were calculated using a one-tailed hypergeometric test. c,d, GREAT analysis of increased peaks in the V.FB1 (c) and V.Endo1 (d) cells from the snATAC-seq. The top relevant GO terms are shown. e, Significant patient-specific receptor–ligand (R–L) pairs under the GO term of angiogenesis. The colour of the bubbles indicates the log10(mean expression) and the size of the bubbles represents the significance in negative log10(one-tailed Wilcoxon test P value + 0.001) from CellPhoneDB. f, Genome browser screenshot of the genomic region upstream of VEGFA. The pseudo-bulk tracks for patient and control samples of V.FB1 from the snATAC-seq and the snRNA-seq are displayed as RPM. The grey shading highlights the promoter region of VEGFA and the yellow shading highlights a potential cis-regulatory enhancer called by the peak-to-gene linkage analysis (orange arc). This potential enhancer region is defined with significantly increased ATAC-seq signal in V.FB1 cells (fold change (COVID-19/control)) = 1.8 and one-tailed Poisson test Padj = 1.26 × 10−5). The y axes for all cell type tracks range from zero to two. Ctrl, control and Cov, COVID-19; cell-type abbreviations as per Fig. 1b.