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 characterised. 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 unique and shared molecular markers of cellular niches and differentiation programmes across oral sites. Using a comparative approach, we identify fibroblast growth factor (FGF) pathway components as potential niche factors for oral epithelial stem cells. Using organoid technology, we validated three FGF ligands (FGF1, FGF7, FGF10) as regulators of site-specific stemness in the dorsal and ventral tongue epithelium. Our dataset of the spatially resolved genes across major oral sites represents a comprehensive resource for unravelling the molecular mechanisms underlying the adult homeostasis of the oral mucosa and its stem cell niches. RNA sequencing data generated using RNA extracted from tissue sections of mouse oral mucosal tissues (tomo-seq)