Prof. Nick BARKER Institute of Molecular and Cell Biology Singapore Link to biosketch

Abstract

Isolating stem cells from human stomach epithelium is challenging due to a lack of useful surface markers. Here, through comparative expression profiling of mouse Lgr5+ adult stem cells along the gastrointestinal tract, we identified novel pylorus-specific stem cell markers, including the membrane protein Aqp5. AQP5+ cells isolated from healthy human pylorus enriched for functional stem cells in organoid assays. Using new Aqp5-driven CreERT2 mouse models to selectively target conditional mutations to the pyloric stem cell compartment in vivo, we established that pyloric stem cells are a source of Wnt-driven, invasive gastric cancer. Furthermore, tumour-resident Aqp5+ cells can selectively initiate cancer organoid growth in vitro, identifying them as potential cancer stem cells. In parallel, we have employed novel gastric epithelial Cre drivers to generate new models of metastatic cancer. Using these new models, we document a key role for tumour-resident Lgr5+ cells in driving gastric cancer progression. These new stem cell markers and mouse models constitute an invaluable resource for deciphering gastric cancer formation and progression.