Acinar Cell Reprogramming: A Clinically Important Target in Pancreatic Disease

Abstract

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.

Keywords::

• acinar to duct cell metaplasia
• MIST1
• NOTCH
• pancreatic cancer
• pancreatitis
• polycomb repressor complex 2
• Type I diabetes

Financial & competing interests disclosure

This work was supported by operating grant R3164A15 from the Canadian Institutes of Health Research, as well as local support from the Children’s Health Research Institute and Lawson Health Research Institute. RM was supported by a postdoctoral fellowship from the Children’s Health Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by operating grant R3164A15 from the Canadian Institutes of Health Research, as well as local support from the Children’s Health Research Institute and Lawson Health Research Institute. RM was supported by a postdoctoral fellowship from the Children’s Health Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.