Extended Data Fig. 4: Transcriptional characterization of virus-induced senescence.
From: Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology
(a) Venn diagram on the left shows 485 differentially expressed genes shared across SARS-CoV-2-infected organoids and postmortem brains of COVID-19 patients defined with a significance adjusted P < 0.05 and log2FC > 0. On the right panel, bar graph indicates the pathways enriched within this 485-gene cohort. Gene Set Enrichment Analysis was carried out using aging hallmark gene sets from the Molecular Signature Database. The statistically significant signatures were selected (P < 0.05, FDR < 0.25). (b) Volcano plots show uninfected versus either Wuhan or Delta-infected brain organoid differential expression of upregulated (blue) and downregulated (red) RNAs (P < 0.05, log2FC > 0). DEG analysis was performed from whole-organoid RNA-seq data and p16-positive senescent-cell regions of interest (ROIs) from NanoString spatial transcriptomic sequencing. (c) Representative images of SARS-CoV-2 nucleocapsid protein immunoreactivity on BOs infected with the indicated SARS-CoV-2 variants and analysed at 5 days post infection. Scale bar, 500 µm. (d) Bar graph shows quantifications of nucleocapsid-positive cells from BOs (n = 4-8) uninfected and infected with the indicated SARS-CoV-2 variants and analysed at 5 dpi. Each data point in the bar graph represents a single organoid analysed. Data are presented as mean values ± s.d.; one-way ANOVA with multiple-comparison post-hoc corrections. (e) SenSig senescence signature heat map gene expression of Delta-infected p16-positive cells.
