Figure 1. Primitive ductules formed in ICC are derived from hepatocytes, rather than cholangiocytes.

(A) Experimental procedure to follow the lineage of hepatocytes and cholangiocytes in mouse liver. In the presence of TM, CreER^T2 expressed from the Alb or CK19 genomic locus translocates into the nucleus and removes the loxP-flanked stop cassette from the R26R allele, leading to permanent heritable expression of the β-gal or YFP gene. (B) Representative images of liver from mice that drank normal water (left) or TAA-containing water (right) for 30 weeks. Tumoral macronodules only formed after TAA administration. (C and D) Immunohistochemical staining of CK19 (C, top row), X-gal staining (C, bottom row), and co-immunofluorescence staining of β-gal and EpCAM (D) were conducted for neoplastic nodules formed in the liver of Alb-CreER^T2;R26R^lacZ/+ mice and CK19-CreER^T2;R26R^lacZ/+ mice after 30 weeks’ TAA administration. DNA was stained with DAPI. Scale bars: 10 mm (B), 100 μm (C), and 50 μm (D).