Although researchers have identified stem cells in several tissues so far, progenitor cells within the stomach have remained elusive. In an advance online publication in Gastroenterology, Deborah Gumucio and her colleagues at the University of Michigan identify a marker that can be used to find and characterize such cells within the stomachs of living mice1. Preliminary evidence suggests that such cells could play a role in some gastric cancers, as the identified cells occur in the same regions where human tumours arise.

The researchers identified the cells as they were working with a line of transgenic mice with a reporter gene for the protein villin. Although villin is not normally expressed in the stomach, the researchers noticed that their villin reporter gene was expressed in a small number of cells in the stomach cavity closer to the oesophagus as well as in another section closer to the intestine. They then examined whether such cells might be the long-elusive stomach stem cells, which they called gastric progenitor cells. Cell lineage assays found that each of the differentiated cells in the new gland had developed from the gastric progenitor cells.

These cells typically remain dormant, the researchers report. However, they divide in response to interferon γ, suggesting that they are activated by pathways that promote inflammation, a process thought to promote gastric cancer. Using an assay that stimulated regeneration of a damaged stomach gland, the researchers showed that these cells were multipotent, capable of regenerating all of the cells within a single gland in the stomach lining.

Surprisingly, they also found most of these progenitor cells in the lower layer of the stomach glands. Previously researchers in the field had supposed that such stem cells would need to located higher in the gland among the cells which renew the stomach lining every 20 to 100 days. In addition, the absence of these cells from glands in other areas of the stomach suggests that other types of stomach stem cells could be lurking in other portions of the organ.

Because of their response to inflammatory factors and their localisation in sites where many stomach cancers develop, these stem cells may have a role in the disease. A known risk factor, infection with Helicobacter pylori stimulates inflammation in the stomach. Among other studies, the researchers are currently looking at the lineages of gastric cancers in mice to figure out whether these gastric progenitor cells are “good guys” or “bad guys” in the genesis of tumours.