LAUSR

The pancreas consists of several specialized cell types which display a remarkable ability to alter cellular identity in injury, regeneration, and repair. The abundant cellular plasticity within the pancreas appears to be exploited in tumorigenesis, with metaplastic, dedifferentiation, and transdifferentiation processes central to the development of pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary neoplasms (IPMNs), precursor lesions to pancreatic ductal adenocarcinoma (PDAC). In the face of shifting cellular identity, the cell-of-origin of pancreatic cancer has been difficult to elucidate. However, with the extensive utilization of in vivo lineage-traced mouse models coupled with insights from human samples, it has emerged that the acinar cell is most efficiently able to give rise to both IPMN and PanIN but that acinar and ductal cells can undergo malignant transformation to PDAC. In this review, we discuss the cellular reprogramming that takes place in both the normal and malignant pancreas and evaluate the current state of evidence that implicate both the acinar and ductal cell as context-dependent origins of this deadly disease.