NOTCH1 and cyst: We recently described that when Jnk∆hepa mice are treated with a single dose of the carcinogen diethylnitrosamine (DEN), and then chronically challenged with CCl4 (DEN/CCl4 model), instead of hepatocellular carcinomas, these animals develop cyst-like structures with molecular features compatible with cholangioma and malignant CCA [1,17], including upregulated expression of NOTCH1, GS and markers of oval cells (Ck19, Sox9, Yap1 mRNA), as well as increased proliferation measured as Pcna mRNA levels (Supplementary Figure S8A–I), similar to those observed now in response to TAA.