Fig. 3. Villin-Cre-based lineage tracing reveals that acinar cells transdifferentiate into ductal cells. Pancreatic epithelium from Villin-Cre;R26R mice was isolated and fixed immediately after plating (A,C,E) or after culture in the presence of TGF for 5 days (B,D,F). On day 0, most cells (A) contained ß-gal activity (blue) and were amylase positive (C) and cytokeratin negative (E), confirming that ß-gal expression was confined to acinar cells. A small percentage of cells did not display ß-gal activity, and most of these cells were positive for the ductal cytokeratins (arrows in C and E). Following 5 days of TGF treatment, most cells were still ß-gal positive (B). No intact amylase-positive cells were observed (D) and ß-gal activity was present in cells expressing ductal cytokeratins (F), indicating that the ß-gal-expressing acinar cells had transdifferentiated into ductal cells. Scale bars: 100 µm in A,B; 10 µm in C-F.