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

胰腺再生过程的特点是腺泡细胞全面重新编程为具有增殖能力的祖细胞样细胞表型。在生理条件下，细胞会再生回腺泡细胞，以恢复胰腺的完整性。这表明，暂时性的所谓腺泡-导管化生(ADM)细胞状态保留了最初分化轮廓的表观遗传记忆，以重建腺泡细胞的身份。在小鼠模型上的实验表明，ADM细胞对致癌的KrasG12D驱动的转化高度敏感，从而触发肿瘤的发展。因此，我们推测KrasG12D的表达消除了腺泡细胞谱系的表观遗传记忆，使ADM细胞处于持续的祖细胞样状态，并将它们重新引导至致瘤转化。

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.