Integrated Multi-Omics Profiling Of Early Human Tooth Development

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 local- ization. Dynamic changes in epithelial-mesenchymal interactions across developmental stages were charac- terized. Secretome analysis confirmed the extensive paracrine signaling from the epithelial to mesenchymal compartments and uncovered signaling factors produced by dental epithelium (DE) that regulate mesen- chymal 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.