Mouse stomachs can be divided into the forestomach (formed from keratinised squamous epithelium), the corpus (composed from glandular epithelium that differentiates into mucous pit cells, parietal cells and zymogenic cells) and the antrum (composed of pit cells and mucous neck cells derived from the glandular epithelium). Although several epithelial stem cell populations have been defined in the adult stomach, the identity of embryonic gastric epithelial progenitors is unknown. Natalia Soshnikova and colleagues’ new study employs single-cell sequencing and lineage tracing in vivo and organoid cultures, to determine the regulation of gastric epithelial progenitors. First, they characterise the composition of the E13.5 embryonic stomach, which contains three distinct, regionalised epithelial-cell types. In the forestomach, Axin2-expressing cells mark a transient population of epithelial progenitors. Moreover, Lgr5-expressing progenitors generate glandular (corpus) and squamous (forestomach) organoids. Through chemical inhibition, the authors show that Wnt and BMP signalling promote Lgr5-expressing cells to undergo zymogenic cell and parietal cell differentiation, respectively, but both pathways block mucous pit cell specification. Finally, Notch signalling is required to maintain progenitor identity and prevent differentiation. Together, these data reveal the presence of heterogeneous progenitor populations in the embryonic stomach that are regulated by distinct signalling networks.
