Tripotent Lgr5 stem cells in the posterior tongue generate non-taste lingual, taste bud and salivary gland cells

<title>Abstract</title> The circumvallate papillae (CVP) and foliate papillae (FoP) of the posterior tongue contain taste buds in close proximity to specialized salivary glands, known as von Ebner and minor salivary glands, respectively. The developmental relationship between taste buds and these salivary glands remains largely unexplored. Lineage tracing studies in mice have revealed that Lgr5 marks taste bud stem cells. Here, we report single-cell RNA sequencing of the entire CVP and FoP of mice, providing a transcriptional atlas of cells from tongue surface epithelium, taste buds and the 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, CVP and FoP harbor chemosensory units composed of taste bud and salivary gland cells derived from the same parental Lgr5+ stem cell.