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Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair

Journal Reference

Stem Cell Res. 2015;15(1):190-202.

Yamaguchi J1, Liss AS1, Sontheimer A1, Mino-Kenudson M2, Castillo CF1, Warshaw AL1, Thayer SP3.

Show Affiliations
  1. Andrew L. Warshaw Institute forPancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
  2. Andrew L. Warshaw Institute forPancreatic Cancer Research, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
  3. Andrew L. Warshaw Institute forPancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA; The University of Nebraska Medical Center (UNMC) Department of Surgery, Division of Surgical Oncology, Omaha, NE, USA. Electronic address: [email protected]

Abstract

Pancreatic duct glands have molecular features known to mark stem cell niches, but their function remains to be determined. To investigate the role of Pancreatic duct glands as a progenitor niche, Pancreatic duct glands were analyzed in both humans and mice. Cells were characterized by immunohistochemistry and microarray analysis. In vivo proliferative activity and migration of Pancreatic duct glands cells were evaluated using a BrdU tag-and-chase strategy in a mouse model of pancreatitis. In vitro migration assays were used to determine the role of trefoil factor (TFF) -1 and 2 in cell migration. Proliferative activity in the pancreatic epithelium in response to inflammatory injury is identified principally within the Pancreatic duct glands compartment. These proliferating cells then migrate out of the Pancreatic duct glands compartment to populate the pancreatic duct. Most of the pancreatic epithelial migration occurs within 5days and relies, in part, on TFF-1 and -2. After migration, Pancreatic duct glands cells lose their Pancreatic duct glands-specific markers and gain a more mature pancreatic  ductal phenotype. Expression analysis of the Pancreatic duct glands epithelium reveals enrichment of embryonic and stem cell pathways. These results suggest that Pancreatic duct glands are an epithelial progenitor compartment that gives rise to mature differentiated progeny that migrate to the pancreatic duct. Thus Pancreatic duct glands are a progenitor niche important for pancreatic epithelial regeneration.

Copyright © 2015. Published by Elsevier B.V.

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