Extended Data Fig. 8: cGAS-STING signalling drives senescence-traits and age-related pathology downstream of YAP/TAZ inactivation in connective tissues.
From: YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS–STING
a, Representative ISH for Mmp3 (Scale bar,10 µm) in the dermis from mice of the indicated genotypes. b, c, Quantification (n = 5 mice per column) of the ISH signal for the indicated SASP markers in the dermis (b, related to a, and to Fig. 4i) and aorta (c, related to Fig. 4j) from mice of the indicated genotypes. Data are presented as mean ± s.d.; P values are derived from two-sided, unpaired t-test. d, RT-qPCR analysis showing induction of SASP marker genes in aortic mediae of SMC-Y/T cKO mice, prevented by STING loss-of-function mutation (SMC-Y/T cKO; STINGGt/Gt). Data (n = 8 mice per column) are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. e, f, Representative ISH for Il1b (e, Scale bars, 10 µm) and quantification (f, n = 5 mice) of the ISH signal for the indicated SASP markers in kidney sections from young control, Y/T cKO and Y/T cKO; STINGGt/Gt mice. Quantification data are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. Related to Fig. 4k. g, Quantification of Vimentin-positive cells (n = 4 mice per column), subcutaneous fat layer thickness (n = 3 mice) and hair follicle density (n = 4 mice) in skin sections of mice of the indicated genotypes. Related to Fig. 4l. Data are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. h, Quantification of medial layer thickness, adventitial layer thickness and elastic lamellae fragmentation of aortic sections from mice of the indicated genotypes. Related to Fig. 4m. Data (n = 5 mice per column) are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test.i, j, Representative elLam staining (i, Scale bar, 100 µm) and quantification (j, n = 4 mice per column) of medial layer thickness, adventitial layer thickness and elLam fragmentation in aortic sections from control mice, and SMC-Y/T cKO mice either treated with Vehicle or with the STING inhibitor C-176. Data are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. k, l, Representative images of H&E-stained (k, Scale bar, 100 µm) kidney sections of mice of the indicated genotype. Quantification (l) of intratubular casts (n = 5 mice per column), dilated tubules (n = 6 mice per column) shown in k, and sclerotic glomeruli shown in Fig. 4n (n = 5 for mice per column) are presented as mean ± s.d.; P values are derived from one-way ANOVA with Dunnett’s multiple comparison test. m, Quantification of γH2AX signal in dermal fibroblasts of control and YAP/TAZ cKO mice. The number of cells analyzed for each condition is reported in the corresponding source data file (n > 150 cells). Data are shown as mean ± s.d.; P values are derived from two-sided, unpaired t-test.
