Tripotent Lgr5 stem cells in the posterior tongue generate lingual, taste, and salivary gland lineages.

The circumvallate papillae and foliate papillae of the posterior tongue contain taste buds in close proximity to specialized salivary glands, known as von Ebner glands. The developmental relationship between taste buds and these salivary glands has been suggested but remains largely unexplored at postnatal and adult stages. Lineage tracing studies in mice have revealed that Lgr5 marks taste bud stem cells. Here, we report single-cell RNA sequencing of the entire circumvallate and foliate papillae of mice, providing a transcriptional atlas of cells from tongue surface epithelium, taste buds, and the associated and non-associated salivary glands. We unveil a developmental trajectory in which taste buds, the associated salivary glands, and the non-taste tongue surface epithelium originate from a common Lgr5 cell. We confirm this tripotency at the clonal level in vitro and with multicolor lineage tracing in vivo. Thus, the circumvallate and foliate papillae harbor chemosensory units composed of taste bud and salivary gland cells derived from the same parental Lgr5-positive stem cell.