Determining the cellular decision of pancreatic acinar cells undergoing a transient regeneration program or persistent tumorigenesis.

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The pancreas regeneration process is characterized by comprehensive reprogramming of the acinar cells towards a progenitor-like cellular phenotype with proliferation capacities. Under physiological conditions, the cells regenerate back to acinar cells to restore pancreas integrity. This indicates that the transient so-called acinar-to-ductal metaplasia (ADM) cell status retains an epigenetic memory of the initial differentiation profile to re-establish acinar cell identity. Experiments in mouse models have shown that ADM cells are highly susceptible towards oncogenic KrasG12D-driven transformation triggering tumor development. Thus, we speculate that the expression of KrasG12D erases the epigenetic memory of the acinar cell lineage, which keeps ADM cells in a persistent progenitor-like state and reroutes them towards tumorigenic transformation.