Fig. 4: Transcriptional changes in human islets after SARS-CoV-2 infection.
From: SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas
Human pancreatic islets of donors 2 and 3 were infected with SARS-CoV-2 and cultivated with or without 5 µM remdesivir, or left uninfected, and prepared for RNA-seq. a, Smart-seq2 expression heatmap illustrating proximity between different treatment conditions and experiments (n = 2 islet donors). b,c, Volcano plots with depicted genes of interest for comparison of islets infected with SARS-CoV-2 and uninfected (b) or remdesivir-treated (c) islets. Significant genes were highlighted in blue (adjusted P < 0.1) and significant genes with a log2(fold-change) > |1| in red. Statistical significance was tested using DESeq2 (ref. 104). d,f, Selection of significantly enriched gene sets comparing differentially expressed genes in islets infected with SARS-CoV-2 versus uninfected (d) or versus remdesivir-treated (f) islets in overrepresentation analyses against common databases; the enrichment test for significance was performed using g:Profiler105. e,g, Selection of significantly enriched gene sets in overrepresentation analyses against COVID-19-related disease terms comparing differentially expressed genes in islets infected with SARS-CoV-2 versus uninfected (e) or versus remdesivir-treated (g) islets; the enrichment test for significance was performed using EnrichR106 (***adjusted P < 0.001, **adjusted P < 0.01, *adjusted P < 0.05). h,j, Normalized enrichment scores for a selection of gene sets in GSEA of islets infected with SARS-CoV-2 compared to uninfected (h) or to remdesivir-treated (j) islets (FDR; ***P < 0.001, **P < 0.01, *P < 0.05). ROS, reactive oxygen species. i,k, GSEA plots for selected gene sets of islets infected with SARS-CoV-2 compared to uninfected (i) or to remdesivir-treated (k) islets. The false discovery rate (FDR) was determined using the GSEA (Broad Institute) desktop tool107 as detailed in Methods.
