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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE267602 | GEO | 2024/11/14

REPOSITORIES: GEO

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Project description:Fibroblast Growth Factor (FGF) signaling plays an important role in lung organogenesis. Over recent decades, FGF signaling in lung development has been extensively studied in animal models. However, little is known about the expression, localization and functional roles of FGF ligands during human fetal lung development. Therefore, we aimed to determine the expression and function of several FGF ligands and receptors in human lung development. Using in situ hybridization (ISH) and RNA-sequencing, we assessed their expression and distribution in native human fetal lung. Human fetal lung explants were treated with recombinant FGF7, FGF9 or FGF10 in air-liquid interface culture. Explants were analyzed grossly, to observe differences in branching pattern, as well as at the cellular and molecular level. ISH demonstrated that FGF7 is expressed in both the epithelium and mesenchyme; FGF9 is mainly localized in the distal epithelium, whereas FGF10 demonstrated diffuse expression throughout the parenchyma with some expression in the smooth muscle cells (SMCs). FGFR2 expression was high in both proximal and distal epithelial cells as well as the SMCs. FGFR3 was expressed mostly in the epithelial cells, with lower expression in the mesenchyme, while FGFR4 was highly expressed throughout the mesenchyme and in the distal epithelium. Using recombinant FGFs, we demonstrated that FGF7 and FGF9 had similar effects on human fetal lung as on mouse; however, FGF10 caused the human explants to expand and form cysts as opposed to inducing epithelial branching as seen in the mouse. In conjunction with decreased branching, treatment with recombinant FGF7, FGF9 and FGF10 also resulted in decreased double-positive SOX2/SOX9 progenitor cells, which are exclusively present in the distal epithelial tips in early human fetal lung. Although FGF ligand localization may be somewhat comparable between developing mouse and human lungs, their functional roles may differ substantially.

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