Defining the contribution of Troy-positive progenitor cells to the mouse esophageal epithelium

• DOI: 10.1016/j.devcel.2024.03.011
• Publication Date: 2024-04-01T14:38:05Z
• Authors: David Grommisch; Menghan Wang; Evelien Eenjes; Maja Svetličič; Qiaolin Deng; Pontus Giselsson; Maria Genander
• Keywords: Homeodomain Proteins; Mice; Esophagus; Esophageal Mucosa; Stem Cells; Animals; Homeostasis; Cell Differentiation; Cell Lineage; Epithelium; Cell Proliferation

AbstractProgenitor cells adapt their behavior in response to tissue demands. However, the molecular mechanisms controlling esophageal progenitor decisions remain largely unknown. Here we demonstrate the presence of aTroy(Tnfrsf19)-expressing progenitor subpopulation localized to defined regions along the mouse esophageal axis. Lineage tracing and mathematical modelling demonstrate thatTroy-positive progenitor cells are prone to undergoing symmetrical fate choices and contribute to esophageal tissue homeostasis long-term. Functionally, TROY inhibits progenitor proliferation and enables commitment to differentiation without affecting fate symmetry. WhereasTroyexpression is stable during esophageal homeostasis, progenitor cells downregulateTroyin response to tissue stress, enabling proliferative expansion of basal cells refractory to differentiation and reestablishment of tissue homeostasis. Our results demonstrate functional, spatially restricted, progenitor heterogeneity in the esophageal epithelium and identify how dynamic regulation ofTroycoordinates tissue generation.