Pancreatic Acinar Cell Plasticity. Senescense, epitelial-mesenchymal transition and p53

Pancreatic acinar cells display plasticity to acquire distinct differentiation programs, being involved indiseases as chronic pancreatitis and pancreatic ductal adenocarcinoma. This work shows that acinarcells cultured in suspension undergo dedifferentiation, acquiring a pancreatic embryonic progenitorphenotype. Dedifferentiated cells turn on a senescent program, associated with activation of p53 andRas pathways. A similar progenitor‐like phenotype with activation of senescence is present inexperimental chronic pancreatitis. Acinar cultures lacking p53 overcome growth arrest and lose thepancreatic phenotype, undergoing an epithelial‐mesenchymal transition, while maintaining theexpression of pre‐pancreatic endoderm and stem cell markers. In experimental acute pancreatitis,absence of p53 results in increased acinar cell proliferation and delayed regeneration. Our findingssupport a role for acinar cell dedifferentiation in the initiation of pancreatic diseases. A p53‐dependent control of cell growth and epithelial differentiation constitutes a tumor suppressivemechanism that may limit PDAC development.