Zhang Ran, Shen Zongshan, Zhao Zhenni, Gu Xiuge, Yan Tianxing, Wei Wei, Wu Chuan, Xia Jinxuan, Zhang Yuanyuan, Chen Suwen, Ma Linsha, Zhang Dong, Wu Xiaoshan, Sharpe Paul T, Wang Songlin
Beijing Laboratory of Oral Health, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Beijing Laboratory of Oral Health, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
Cell Rep. 2025 Apr 22;44(4):115437. doi: 10.1016/j.celrep.2025.115437. Epub 2025 Mar 20.
The development of early human tooth primordia is not well understood. Here, we linked single-cell RNA sequencing, spatial transcriptomics, and secretome analysis to characterize human fetal tooth development over time. A spatiotemporal atlas of human tooth development at multiple levels was mapped, identifying previously uncharacterized epithelial subpopulations with distinct gene expression profiles and spatial localization. Dynamic changes in epithelial-mesenchymal interactions across developmental stages were characterized. Secretome analysis confirmed the extensive paracrine signaling from the epithelial to mesenchymal compartments and uncovered signaling factors produced by dental epithelium (DE) that regulate mesenchymal cell fate and differentiation. Integration of these datasets highlighted the crucial role of the DE in orchestrating tooth morphogenesis. Our multi-omics approach not only provides unprecedented insights into the cellular and molecular mechanisms of ectoderm-derived tissue development but also serves as a valuable resource, which is publicly available online, for future studies on human tooth regeneration and related diseases.
早期人类牙齿原基的发育尚未得到充分了解。在这里，我们将单细胞RNA测序、空间转录组学和分泌组分析相结合，以随时间推移表征人类胎儿牙齿的发育。绘制了多个水平的人类牙齿发育时空图谱，鉴定出具有不同基因表达谱和空间定位的先前未被表征的上皮亚群。表征了发育阶段上皮-间充质相互作用的动态变化。分泌组分析证实了从上皮到间充质区室的广泛旁分泌信号传导，并发现了由牙上皮（DE）产生的调节间充质细胞命运和分化的信号因子。这些数据集的整合突出了DE在协调牙齿形态发生中的关键作用。我们的多组学方法不仅为外胚层衍生组织发育的细胞和分子机制提供了前所未有的见解，而且还作为一种有价值的资源在线公开提供，以供未来关于人类牙齿再生和相关疾病的研究使用。
