Fig. 3
Yap deletion in Atg7 KO mice attenuates hepatomegaly, altered tissue architecture and hepatocarcinogenesis. a Control and TAM-inducible, hepatocyte-specific Atg7 KO (ERT2-Alb-CRE:Atg7F/F) and Atg7/Yap het DKO (ERT2-Alb-CRE:Atg7 F/F, Yap F/wt) and Atg7/Yap DKO (ERT2-Alb-CRE:Atg7F/F, YapF/F) were analyzed 1 week, 2 weeks, 4 weeks, and 12 months after TAM injection. TAM tamoxifen. N = 15, 12, 17, and 8 animals respectively. b Gross liver morphology in control, Atg7 KO and Atg7/Yap DKO after 12 months of TAM injection. c Liver/body weight ratio 1 week, 2 weeks, 4 weeks, and 12 months after TAM injection of control, Atg7 KO and Atg7/Yap DKO. Stars indicate significant differences between Atg7 KO and Atg7/Yap DKO at the respective time points by one-way ANOVA and Tukey’s HSD. ***P = 0.0001. d Liver/body weight ratio in control, Atg7 KO and Atg7 KO/Yap het DKO, Atg7/Yap DKO mice 12 months after TAM induction. ***P < 0.0005. e Absolute tumor number per mouse in control, Atg7 KO and Atg7 KO/Yap het DKO, Atg7/Yap DKO mice 12 months after TAM induction. f Size of largest tumor size per mouse in control, Atg7 KO and Atg7 KO/Yap het DKO, Atg7/Yap DKO mice 12 months after TAM induction. g Immunostaining for β-catenin, HNF4α, Epcam, Cd44 in controls, Atg7 KO and Atg7/Yap DKO 12 months after TAM injection. Scale bar indicates 100 µm. h Quantitative analysis of individual hepatocyte areas in controls, Atg7 KO and Atg7/Yap DKO 12 months after TAM injection. n = 238, 242, and 273 cells were analyzed, respectively. i Frequency distribution analysis of hepatocyte size in controls, Atg7 KO and Atg7/Yap DKO. j qRT-PCR analysis of whole liver mRNA from control, Atg7 KO, Atg7/Yap DKO for Albumin, Epcam, Cd133, and Cd44, normalized to Tbp expression. N = 7, 12, and 8 animals, respectively. Data represent mean ± SD. P-values analyzed by one-way ANOVA and Tukey’s HSD. *P < 0.05, **P < 0.005, ***P < 0.001, ****P < 0.0001 unless indicated otherwise. ns, not significant
