Signalling codes for the maintenance and lineage commitment of embryonic gastric epithelial progenitors

The identity of embryonic gastric epithelial progenitors is unknown. We used single-cell RNA sequencing, genetic lineage tracing and organoid assays to assess whether Axin2 and Lgr5 expressing cells are gastric progenitors in the developing mouse stomach. We show that Axin2+ cells represent a transient population of embryonic epithelial cells in the forestomach. Lgr5+ cells generate both glandular corpus and squamous forestomach organoids ex vivo. Only Lgr5+ progenitors give rise to zymogenic cells in culture. Modulating the activity of the WNT, BMP and Notch pathways in vivo and ex vivo, we found that WNTs are essential for the maintenance of Lgr5+ epithelial cells. Notch prevents differen…