Acinar cell reprogramming: a clinically important target in pancreatic disease.
Acinar cells of the pancreas produce the majority of enzymes required for digestion and make up >90% of the cells within the pancreas. Due to a common developmental origin and the plastic nature of the acinar cell phenotype, these cells have been identified as a possible source of β cells as a therapeutic option for Type I diabetes. However, recent evidence indicates that acinar cells are the main source of pancreatic intraepithelial neoplasias (PanINs), the predecessor of pancreatic ductal adenocarcinoma (PDAC). The conversion of acinar cells to either β cells or precursors to PDAC is dependent on reprogramming of the cells to a more primitive, progenitor-like phenotype, which involves changes in transcription factor expression and activity, and changes in their epigenetic program. This review will focus on the mechanisms that promote acinar cell reprogramming, as well as the factors that may affect these mechanisms.
Department of Paediatrics, Physiology & Pharmacology, & Oncology, University of Western Ontario, London, ON N6C 2V5, Canada.
Christopher L
CL
Pin
Joanna F
JF
Ryan
Rashid
R
Mehmood
D061354:Acinar Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D044127:Epigenesis, Genetic; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology; D051379:Mice; D010179:Pancreas / Q000166:cytology* / Q000196:embryology; D010182:Pancreatic Diseases; D010183:Pancreatic Ducts / Q000166:cytology; D010190:Pancreatic Neoplasms / Q000209:etiology
MIST1; NOTCH; Type I diabetes; acinar to duct cell metaplasia; pancreatic cancer; pancreatitis; polycomb repressor complex 2