Spatial transcriptomics reveals molecular cues underlying the site specificity of the adult mouse oral mucosa and its stem cell niches.

The oral cavity is a multifunctional organ composed of structurally heterogeneous mucosal tissues that remain poorly characterized. Oral mucosal tissues are highly stratified and segmented along an epithelial-lamina propria axis. Here, we performed spatial transcriptomics (tomo-seq) on the tongue, cheeks, and palate of the adult mouse to understand the cues that maintain the oral mucosal sites. We define molecular markers of unique and shared cellular niches and differentiation programs across oral sites. Using a comparative approach, we identify fibroblast growth factor (FGF) pathway components as potential stem cell niche factors for oral epithelial stem cells. Using organoid-forming efficiency assays, we validated three FGF ligands (FGF1, FGF7, and FGF10) as site-specific niche factors in the dorsal and ventral tongue. Our dataset of the spatially resolved genes across major oral sites represents a comprehensive resource for unraveling the molecular mechanisms underlying the adult homeostasis of the oral mucosa and its stem cell niches.