title: Identification of alanyl aminopeptidase (CD13) as a surface marker for isolation of mature gastric zymogenic chief cells.
abstract: Injury and inflammation in the gastric epithelium can cause disruption of the pathways that guide the differentiation of cell lineages, which in turn can cause persistent alterations in differentiation patterns, known as metaplasia. Metaplasia that occurs in the stomach is associated with increased risk for cancer. Methods for isolating distinct gastric epithelial cell populations would facilitate dissection of the molecular and cellular pathways that guide normal and metaplastic differentiation. Here, we identify alanyl aminopeptidase (CD13) as a specific surface marker of zymogenic chief cells (ZCs) in the gastric epithelium. We show that 1) among gastric epithelial cells alanyl aminopeptidase expression is confined to mature ZCs, and 2) its expression is lost en route to metaplasia in both mouse and human stomachs. With this new marker coupled with new techniques that we introduce for dissociating gastric epithelial cells and overcoming their constitutive autofluorescence, we are able to reliably isolate enriched populations of ZCs for both molecular analysis and for the establishment of ZC-derived ex vivo gastroid cultures.
authors.affiliation: Division of Gastroenterology, Departments of Medicine, Pathology, and Immunology, and Developmental Biology, Washington University, St. Louis, Missouri;
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Moore
authors.affiliation: Division of Gastroenterology, Departments of Medicine, Pathology, and Immunology, and Developmental Biology, Washington University, St. Louis, Missouri;
authors.forename: Ramon U
authors.initials: RU
authors.lastname: Jin
authors.affiliation: Division of Gastroenterology, Departments of Medicine, Pathology, and Immunology, and Developmental Biology, Washington University, St. Louis, Missouri;
authors.forename: Luciana
authors.initials: L
authors.lastname: Osaki
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Noto
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.affiliation: Division of Gastroenterology, Departments of Medicine, Pathology, and Immunology, and Developmental Biology, Washington University, St. Louis, Missouri; jmills@wustl.edu.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Mills
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D019872:Chief Cells, Gastric / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008679:Metaplasia; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D013270:Stomach / Q000201:enzymology* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D002352:Carrier Proteins; C488191:Clnk protein, mouse; D018826:CD13 Antigens
keywords: alanyl aminopeptidase; aminopeptidase N/CD13; gastric epithelium; gastroid; splasmolytic polypeptide expressing metaplasia; zymogenic chief cell