Identification of alanyl aminopeptidase (CD13) as a surface marker for isolation of mature gastric zymogenic chief cells

Am J Physiol Gastrointest Liver Physiol. 2015 Dec 15;309(12):G955-64. doi: 10.1152/ajpgi.00261.2015. Epub 2015 Oct 29.

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.

Keywords: alanyl aminopeptidase; aminopeptidase N/CD13; gastric epithelium; gastroid; splasmolytic polypeptide expressing metaplasia; zymogenic chief cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Biomarkers / metabolism
  • CD13 Antigens / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Separation / methods*
  • Cells, Cultured
  • Chief Cells, Gastric / enzymology*
  • Chief Cells, Gastric / pathology
  • Female
  • Humans
  • Male
  • Metaplasia
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Stomach / enzymology*
  • Stomach / pathology

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Carrier Proteins
  • Clnk protein, mouse
  • CD13 Antigens