Figure 3. Notch signal activation is significant not only for conversion of hepatocytes into biliary lineage cells at the onset of ICC, but also the malignancy and progression of ICC.

(A–C) Immunofluorescence staining of CK19 was conducted in the liver of R26R^Notch/+ mice (A), Alb-CreER^T2;R26R^Notch/+ mice (B), and Alb-CreER^T2;Hes1^fl/fl mice (C) after 14 weeks of TAA administration. (D) The percentages of cells immunoreactive for CK19 in the liver of R26R^Notch/+, Alb-CreER^T2;R26R^Notch/+, and Alb-CreER^T2;Hes1^fl/fl mice were calculated after counting approximately 3,000 cells per field of vision in 3 discontinuous liver tissue slides for 3 individual mice after 14 weeks of TAA administration. The data represent mean ± SD. (E) Immunofluorescence staining of CK19 was conducted in the liver of Alb-CreER^T2;R26R^YFP/Notch mice after 8 weeks of TAA administration. (F and G) Representative images of the liver from R26R^Notch/+ mice (F) and Alb-CreER^T2;R26R^Notch/+ mice (G) after 14 weeks of TAA administration. Developing neoplastic nodules are only found in the liver of Alb-CreER^T2;R26R^Notch/+ mice. CV, central vein; PV, portal vein. DNA was stained with DAPI. Scale bars: 500 μm (A–C), 100 μm (E), and 5 mm (F and G).