Hereditary Chronic Pancreatitis Induced Plasticity Cooperates with Mutant Kras in Early Pancreatic Carcinogenesis
Hereditary chronic pancreatitis (CP) increases the risk of pancreatic cancer, but the mechanisms by which chronic inflammation influences oncogene-driven pancreatic carcinogenesis remain poorly understood. A recently developed mouse model of CP, carrying the human Carboxypeptidase A1 (CPA1) p.N256K mutation, offers a valuable platform for uncovering the molecular processes linking chronic inflammation to pancreatic carcinogenesis. To investigate the impact of chronic inflammation on pancreatic cancer initiation, we crossed Cpa1N256K mice (Cpa1) with the pancreatic cancer model Ptf1aCre;KrasLSL-G12D (KC). In Cre, Cpa1, KC and KC-Cpa1 mice, we performed phenotypic characterization at different ages using histological, RNA sequencing and single-cell RNA-sequencing analyses. Overall design: Single cells and total RNA from pancreata of Cre, Cpa1, KC and KC-Cpa1 mice were isolated at different ages.