Abstract C072: Bmi1 expression is upregulated in response to injury/stress in the pancreas

Abstract Pancreatic homeostasis is regulated in part through epigenetic mechanisms that restrict or enable access of pancreatic lineage transcription factors to their target genes. These epigenetic protein cascades are also required for regeneration of the pancreas after injury. B-cell Moloney murine leukemia virus integration site 1 (Bmi1), a central protein in the Polycomb repressor complex 1 (PRC1), has been shown to be required for the regeneration of the pancreas after injury and its absence prevents pancreatic neoplasia in mice. Previous work also suggests that Bmi1 marks a subset of acinar cells contributing to pancreatic renewal and tissue maintenance. It remains unclear how Bmi1 expression levels are regulated in response to pancreatic stress and injury. Here we assess the baseline expression of Bmi1 in pancreatic tissue with a genetic reporter mouse model as well as changes in Bmi1 mRNA levels at different time points after the induction of pancreatitis in wild-type mice via RNA in situ hybridization (RNAscope). We also compare the ability of the murine pancreas to regenerate after acute pancreatitis in the presence and absence of Bmi1. Our data indicates that rather than a specific subpopulation, most, if not all, acinar cells in the pancreas express Bmi1 during their life and specific loss of Bmi1 in the pancreas impairs regeneration after acute pancreatitis. We also show an increase in Bmi1 mRNA levels within the pancreas shortly after the induction of acute pancreatitis which reduces as the pancreas resumes its normal histology. Altogether, our data indicate that Bmi1 expression is dynamic, responsive to injury and necessary for pancreatic homeostasis and regeneration. Citation Format: Nur Muhammad Renollet, Joyce K Thompson, Emily Wu, Osama Alkhalili, Nina Steele, Filip Bednar. Bmi1 expression is upregulated in response to injury/stress in the pancreas abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84 (17 Suppl₂): Abstract nr C072.