Abstract
Recent studies of epithelial tissues have revealed the presence of tissue-specific stem cells that are able to establish multiple cell lineages within an organ. The stem cells give rise to progenitors that replicate before differentiating into specific cell lineages. The mechanism by which homeostasis is established between proliferating stem or progenitor cells and terminally differentiated cells is unclear. This study demonstrates that Agr2 expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while also inhibiting the proliferation of stem or progenitor cells. When Agr2 expression is absent, gastric mucous neck cells increased in number as does the number of proliferating cells. Agr2 expression loss also resulted in the decline of terminally differentiated cells, which was supplanted by cells that exhibited nuclear SOX9 labeling. Sox9 expression has been associated with progenitor and stem cells. Similar effects of the Agr2 null on cell proliferation in the intestine were also observed. Agr2 consequently serves to maintain the balance between proliferating and differentiated epithelial cells.
Highlights
The in vivo function of the adenocarcinoma-associated gene, Anterior gradient 2 (Agr2), is not known in the stomach
This study demonstrates that Agr2 expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while inhibiting the proliferation of stem or progenitor cells
Agr2 expression loss resulted in the decline of terminally differentiated cells, which was supplanted by cells that exhibited nuclear SOX9 labeling
Summary
The in vivo function of the adenocarcinoma-associated gene, Agr, is not known in the stomach. Significance: Agr functions in regulating homeostasis between differentiating and proliferating cells in the stomach. This study demonstrates that Agr expression by mucous neck cells in the stomach promotes the differentiation of multiple cell lineages while inhibiting the proliferation of stem or progenitor cells. The pit layer is the isthmus, where putative stem and progenitor cells that give rise to all gastric cell lineages reside [2,3,4,5,6]. Proliferating cells allegedly representing stem and progenitor cells in the antrum reside in the isthmus region just above the base of the antral gland. Agr Knockout Disrupts Gastric Cell Homeostasis sistent with a role for Agr in regulating cell proliferation, differentiation, and homeostasis among the different cell lineages in the mouse glandular stomach. The resultant mouse expressed a phenotype that was most pronounced in the stomach and was con-
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