Metaplasia-induced Epithelial Heterogeneity Directs Pancreatic Injury and Tumorigenesis.

ADM under conditions of chronic injury results in the formation of a pyloric-type metaplasia which seeds disparate tuft and EEC lineages. This carefully orchestrated plasticity generates myriad epithelial cell types which likely mitigate injury, providing protection from the formation of pancreatitis and PDAC. Kras expression is sufficient to drive neoplasia when targeted to injury-induced ADM populations offering an alternative origin for tumorigenesis. This program is conserved in human pancreatitis and provides insight into early events in pancreas diseases.