Fig. 2.

Integrin αvβ6 is expressed by an actively proliferating subset of hepatic progenitor (oval) cells in Mdr2^−/− mice. Double staining for αvβ6 integrin and hepatic progenitor (oval) cell markers A6 (A) and Trop2 (B). Original magnification ×100. (C) Nuclei within αvβ6-positive pseudoducts are frequently positive for the cell proliferation marker proliferating cell nuclear antigen (arrows), indicating that the αvβ6⁺ subset of progenitor cells actively proliferates (double-immunofluorescence for αvβ6 [red] and proliferating cell nuclear antigen [green]). Original magnification ×630. (D) Cell colonies derived from EpCAM⁺ progenitor (oval) cells express αvβ6 integrin and up-regulate both cholangiocyte (HNF1β, CK19) and hepatocyte (HNF4α, albumin) lineage differentiation markers in vitro. Primary EpCAM⁺ cells were isolated from Mdr2^−/− mice and cultured for up to 14 days, as described in Materials and Methods. Original magnification ×200. Data are expressed as mean ± standard error of the mean relative to day 0 (from four individual mice). *P < 0.05. Abbreviations: DAPI, 4′,6-diamidino-2-phenylindole; K19, cytokeratin 19; PCNA, proliferating cell nuclear antigen.