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 epitheliallamina 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)口腔是一类由结构异质性黏膜组织构成的多功能器官，目前对其分子特征的认知仍较为有限。口腔黏膜组织呈高度分层结构，并沿上皮固有层（epithelial lamina propria）轴进行分区。本研究针对成年小鼠的舌、颊部及腭部组织开展空间转录组学（spatial transcriptomics，tomo-seq）分析，以解析维持口腔黏膜区域特征的调控信号。我们鉴定了不同口腔黏膜区域中细胞微环境（cellular niches）与分化程序的特异性及共有分子标记物。通过比较分析策略，我们发现成纤维细胞生长因子（fibroblast growth factor, FGF）通路相关组分可作为口腔上皮干细胞的潜在微环境调控因子。借助类器官（organoid）技术，我们验证了三种FGF配体（FGF1、FGF7、FGF10）可调控舌背与舌腹上皮的区域特异性干细胞干性。本研究生成的覆盖主要口腔黏膜区域的空间分辨率基因表达数据集，可为解析成年口腔黏膜稳态及其干细胞微环境的分子机制提供全面的研究资源。该数据集的RNA测序数据源自小鼠口腔黏膜组织切片提取的总RNA，采用tomo-seq技术完成。