Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair
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 analys...
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2015-07-01
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doaj-ccd2aa3f97f54192a882e309ffe789032020-11-24T23:02:50ZengElsevierStem Cell Research1873-50611876-77532015-07-0115119020210.1016/j.scr.2015.05.006Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repairJunpei Yamaguchi0Andrew S. Liss1Alexandra Sontheimer2Mari Mino-Kenudson3Carlos Fernández-del Castillo4Andrew L. Warshaw5Sarah P. Thayer6Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USAAndrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USAAndrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USAAndrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Pathology, Massachusetts General Hospital, Boston, MA, USAAndrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USAAndrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USAAndrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USAPancreatic 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 5 days 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.http://www.sciencedirect.com/science/article/pii/S1873506115000653 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Junpei Yamaguchi Andrew S. Liss Alexandra Sontheimer Mari Mino-Kenudson Carlos Fernández-del Castillo Andrew L. Warshaw Sarah P. Thayer |
spellingShingle |
Junpei Yamaguchi Andrew S. Liss Alexandra Sontheimer Mari Mino-Kenudson Carlos Fernández-del Castillo Andrew L. Warshaw Sarah P. Thayer Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair Stem Cell Research |
author_facet |
Junpei Yamaguchi Andrew S. Liss Alexandra Sontheimer Mari Mino-Kenudson Carlos Fernández-del Castillo Andrew L. Warshaw Sarah P. Thayer |
author_sort |
Junpei Yamaguchi |
title |
Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair |
title_short |
Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair |
title_full |
Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair |
title_fullStr |
Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair |
title_full_unstemmed |
Pancreatic duct glands (PDGs) are a progenitor compartment responsible for pancreatic ductal epithelial repair |
title_sort |
pancreatic duct glands (pdgs) are a progenitor compartment responsible for pancreatic ductal epithelial repair |
publisher |
Elsevier |
series |
Stem Cell Research |
issn |
1873-5061 1876-7753 |
publishDate |
2015-07-01 |
description |
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 5 days 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. |
url |
http://www.sciencedirect.com/science/article/pii/S1873506115000653 |
work_keys_str_mv |
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