title: Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair.
abstract: Pancreatic duct glands (PDGs) have molecular features known to mark stem cell niches, but their function remains to be determined. To investigate the role of PDGs as a progenitor niche, PDGs were analyzed in both humans and mice. Cells were characterized by immunohistochemistry and microarray analysis. In vivo proliferative activity and migration of PDG 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 PDG compartment. These proliferating cells then migrate out of the PDG 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, PDG cells lose their PDG-specific markers and gain a more mature pancreatic ductal phenotype. Expression analysis of the PDG epithelium reveals enrichment of embryonic and stem cell pathways. These results suggest that PDGs are an epithelial progenitor compartment that gives rise to mature differentiated progeny that migrate to the pancreatic duct. Thus PDGs are a progenitor niche important for pancreatic epithelial regeneration.
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Junpei
authors.initials: J
authors.lastname: Yamaguchi
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Liss
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sontheimer
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Carlos Fernández-Del
authors.initials: CF
authors.lastname: Castillo
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Warshaw
authors.affiliation: Andrew L. Warshaw Institute for Pancreatic 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: sarah.thayer@UNMC.edu.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Thayer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010183:Pancreatic Ducts / Q000166:cytology*; D010455:Peptides / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000071164:Trefoil Factor-2; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D010455:Peptides; D000071164:Trefoil Factor-2; D012313:RNA