Gastric Epithelial Stem Cells

Abstract

Advances in our understanding of stem cells in the gastrointestinal tract include the identification of molecular markers of stem and early progenitor cells in the small intestine. Although gastric epithelial stem cells have been localized, little is known about their molecular biology. Recent reports describe the use of inducible Cre recombinase activity to indelibly label candidate stem cells and their progeny in the distal stomach, (ie, the antrum and pylorus). No such lineage labeling of epithelial stem cells has been reported in the gastric body (corpus). Among stem cells in the alimentary canal, those of the adult corpus are unique in that they lie close to the lumen and increase proliferation following loss of a single mature progeny lineage, the acid-secreting parietal cell. They are also unique in that they neither depend on Wnt signaling nor express the surface marker Lgr5. Because pathogenesis of gastric adenocarcinoma has been associated with abnormal patterns of gastric differentiation and with chronic tissue injury, there has been much research on the response of stomach epithelial stem cells to inflammation. Chronic inflammation, as induced by infection with Helicobacter pylori, affects differentiation and promotes metaplasias. Several studies have identified cellular and molecular mechanisms in spasmolytic polypeptide–expressing (pseudopyloric) metaplasia. Researchers have also begun to identify signaling pathways and events that take place during embryonic development that eventually establish the adult stem cells to maintain the specific features and functions of the stomach mucosa. We review the cytologic, molecular, functional, and developmental properties of gastric epithelial stem cells.

Gastric Cancer: A Stem Cell Disease?

“…Nevertheless, it appears that some Runx1-expressing cells are stem cells, whereas others are diferentiated cells, such as pit cells. Moreover, 80% of eR1 Additional markers have been proposed for gastric stem cells (e.g., DCKL1/DCAMKL1, CD133/PROM1, and CD44), but the multipotency of these cells has not yet been analyzed by lineage tracing [15,16]. Khurana et al found that CD44 (cluster of diferentiation 44) is mainly expressed at the base of antral/pyloric glands, in a region overlapping Lgr5, and in the isthmus region of the corpus glands [17,18].…”

Gastric cancer stem cells: therapeutic targets

“…Regulating the CSC microenvironmental niche SCs in normal gastric mucosa are thought to populate the proliferative zone in the neck-isthmus region [6,131]. Crypts in the stomach may act as niches for SCs, where surrounding structures and arising interactions contribute to the maintenance of stem/progenitor cell proliferation and differentiation [23,131].…”

“…Crypts in the stomach may act as niches for SCs, where surrounding structures and arising interactions contribute to the maintenance of stem/progenitor cell proliferation and differentiation [23,131]. It has been suggested that CSCs reside only in designated conditioned compartments with an adequate cancer cell-stroma interface [23,132].…”

A candidate gastric stem/progenitor cell marker revealed by genome‐wide analysis

“…Furthermore, it is becoming established that gastric units are monoclonal in origin [4]. Therefore, there is a consensus that all gastric epithelial cells originate from multi-potential stem or progenitor cells [5]. Indeed, lineage-tracing studies with chemical mutagenesis or Sox2 expression have demonstrated the existence of multi-potent stem cells in the rodent stomach [6,7].…”

“…Previous studies have pinpointed the gland isthmus as the gastric stem cell zone, based on the abundant cellular proliferation and enrichment of immature, granule-free cells within the cycling population. Rare gastric stem cells in the isthmus presumably undergo transit amplification and contribute to the continuous bidirectional renewal of differentiated gastric epithelial cells [5,13]. Nevertheless, the marker genes and molecular characteristics of gastric stem cells are extremely elusive.…”