Fig 2: Identification of candidate YAP/TAZ/TEAD target genes in hypoxia-responsive genes in MCF7 and HCC1143 cells. (A,B) Heatmaps showing intersection of TempO-Seq data for hypoxia-regulated genes in MCF7 and HCC1143 cells with YAP/TAZ/TEAD target genes reported in literature (A; [36,37]) and candidate TEAD1-4-binding genes identified using DoRothEA (B; [38]). Values are Log2 fold change under hypoxia relative to normoxia. Genes labeled green in (A) or labeled blue in (B) are shared between MCF7 and HCC1143 in the respective analyses. Genes labeled red in (A) and (B) are shared in both analyses for both cell lines. (C) Venn diagram showing distinct and overlapping hypoxia regulated genes for MCF7 and HCC1143 identified both in literature and by DoRothEA.

Fig 3: There is no significant difference in infection severity between Cre(−) and Cre(+) YAP/TAZ△LEC littermates after influenza challenge. (A) Weight change for C57Bl/6 mice and Cre(−) and Cre(+) YAP/TAZ△LEC littermates after saline or influenza challenge. Mean and SEM are shown. (B) Influenza PFU recovered from left lobes of Cre(−) or Cre(+) littermates at 7 dpi after influenza challenge. Median and IQR are shown for n = 12 mice per group. Statistical significance by unpaired two-tailed Mann Whitney test. (C) Nucleoprotein (NP) mRNA was quantified from left lobes collected from Cre(−) or Cre(+) littermates at 7 dpi after influenza infection. Median and IQR are shown for n = 16–17 mice per group. Statistical significance by unpaired two-tailed Mann Whitney test. (D,E) Histopathological scoring by a blinded veterinary pathologist was performed using H&E-stained lung sections from Cre(−) or Cre(+) littermates at 7 dpi after influenza infection; representative sections are shown. Mean and SD are shown for n = 3 mice per group. Statistical significance by unpaired two-tailed Mann Whitney test.

Fig 4: Progressive myofibroblast YAP/TAZ activation occurs during human kidney fibrogenesis.(A) Serial biopsies collected from the same renal allograft at different times intratransplant and after transplant revealed a progressive increase in interstitial fibrosis, as evidenced by increased picrosirius red staining over time. Black arrows point to increased deposition of collagen (pathologic matrix), whereas black arrowheads identify tubular basement membrane. Black scale bar: 100 μm. (B) Kidney sections were costained with antibodies directed against α-smooth muscle actin (α-SMA, green) and YAP (red) with DAPI (blue) nuclear counterstaining. Each dot in the graph represents a single image (n = 5 images day 0, n = 13 images day 9, and n = 12 images month 2). White arrows point to α-SMA+ myofibroblasts with predominantly nuclear YAP staining. White scale bar: 25 μm. The percentage of α-SMA+ myofibroblasts with predominantly nuclear YAP staining was quantified. (C) Kidney sections were similarly analyzed for nuclear TAZ localization in α-SMA+ myofibroblasts (α-SMA: green, TAZ: red, DAPI: blue). Each dot in the graph represents a single image (n = 4 images day 0, n = 5 images day 9, and n = 11 images month 2). White scale bar: 25 μm. One-way ANOVA with post hoc Tukey’s test was used for comparisons. Data shown as mean ± SEM. *P < 0.05.

Fig 5: Tumor features in Yap or Taz-depleted Akt/NRas murine livers. (A) Representative images of gross images, H&E staining, and immunohistochemistry for Ki67 and cytokeratin 19 (Ck19). Scalebar: 200 μm for magnification of 100×, 100 μm for magnification of 200×. (B) Percentages of Ck19-positive area in the 2 groups. (C) Percentage of Ki67-positive cells in tumors.