Extended Data Fig. 7: YAP/TAZ loss induces SASP induction through cGAS/STING signalling.
From: YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS–STING
a–c, Heatmap showing the STING-dependent induction of inflammatory genes (a), interferon target genes (b) and NF-kB target genes (c) upon YAP/TAZ depletion in WI-38 fibroblasts, as determined by RNA-seq. d, Heatmap showing that E2F target genes are downregulated upon YAP/TAZ depletion in WI-38 cells independently of STING, as determined by RNA-seq. e, Heatmap portraying the STING-signaling dependency of SASP marker induction upon genetic ablation of YAP/TAZ (Y/T cKO) in primary MAFs. STINGi is H-151 (1 µM). f, Heatmap displaying cGAS-dependent cytokine secretion upon genetic ablation of YAP/TAZ in primary MAFs. g, RT-qPCR for SASP marker genes upon YAP/TAZ depletion (siY/T) in mouse aortic smooth muscle cells, with or without concomitant cGAS (sicGas#1 and #2) or STING (siSting#1 and #2) depletion. Data (n = 3 independent experiments) are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. h, Cytokine array showing cGAS-dependent secretion of the indicated SASP cytokines upon YAP/TAZ ablation in primary mouse aortic smooth muscle cells. Spots in the upper left and right corners and in the lower right corner served as reference. i, In situ hybridization for CXCL10 in control (siCo) and YAP/TAZ-depleted (siY/T) WI-38 cells, expressing EGFP-cGAS reporter. Treatment with STING inhibitor (STINGi, 1 µM H-151 for 48 h) served as negative control. Scale bar, 2 μm. Percentage of cells showing concomitant EGFP-cGAS activation and CXCL10 mRNA expression were 0% in siCo, 35% in siY/T and 0% in siY/T + STINGi conditions. At least 40 cells were analyzed for each condition. j, Upper panel, RT-qPCR for SASP marker genes in YAP/TAZ-depleted (siY/T) and control (siCo) WI-38 cells, treated with 2',3'-dideoxycytidine (ddC, 5 µM for 1 week). Lower panel, qPCR for mitochondrial genes confirming mtDNA depletion by ddC treatment. Note that mtDNA is not required for SASP induction after Y/T depletion. Data (n = 3 independent experiments) are presented as mean ± s.d.
