Plasticity-Driven Regeneration of Circumvallate Papilla After Lgr5+ Stem Cells Loss

Taste receptor cells located within the papillae of the oral cavity have a defined lifespan of 8-12 days. They are continuously replenished by a pool of stem/progenitor cells residing outside the taste buds. Previous studies have identified Lgr5 positive stem/progenitor cells localized within the basal trench of the circumvallate papilla (CVP) as the source of all taste and non-taste epithelial cells. However, it remains unclear whether an alternative stem cell population within the CVP can regenerate the epithelium in the absence of Lgr5-expressing cells. Using Lgr5^DTR mice in which Lgr5-expressing cells were selectively ablated via diphtheria toxin administration, we observed a substantial loss of these cells in the CVP, leading to rapid degeneration of taste buds, K8-expressing taste receptor cells, basal cells, and the basement membrane within 24 h post-injection. Notably, while the basal cells and basement membrane were fully regenerated at 72 h post-injection, taste buds reappeared at 2 weeks. Previous studies have demonstrated that SOX10-Cre-labeled cells originating from Von Ebner's gland (VEG) contribute to the CVP epithelium and are detected within the taste bud. However, the cellular dynamics and mechanistic role of these SOX10-Cre-labeled cells in the maintenance of taste buds remain unclear. Lineage tracing results revealed that K8/K14-expressing cells from the ducts of VEG contribute to the regeneration of taste buds, indicating that these duct-associated epithelial cells contribute to regeneration, potentially through injury-induced cellular plasticity in the absence of a resident Lgr5-expressing stem cell population.