Transcriptomic regulation of pancreatic acinar cell homeostasis and plasticity

Pancreatic acinar cells are highly specialized secretory epithelial cells in which coordinated transcriptional, epigenetic, and post-transcriptional regulatory mechanisms maintain digestive enzyme production, polarized architecture, and lineage fidelity. This homeostatic network preserves acinar identity while enabling rapid adaptation to physiological stress. Disruption of these regulatory mechanisms triggers acinar-to-ductal metaplasia (ADM), a reversible reprogramming state that supports acinar cell survival and regeneration after acute injury. However, if ADM persists under chronic inflammation or oncogenic KRAS activation, it can facilitate the initiation of pancreatic ductal adenocarcinoma. Elucidating these mechanisms offers opportunities to restore acinar cell homeostasis, reverse ADM, and prevent neoplastic transformation. In this review, we summarize current knowledge on the transcriptional, epigenetic, and post-transcriptional regulation of acinar cell homeostasis and plasticity, with emphasis on their roles in ADM.