Work

Integrative Spatial and Single-Nucleus Transcriptomics Elucidate Cell Lineage Dynamics in Human Tooth Morphogenesis

Year: 2025

Type: article

Abstract: INTRODUCTION AND AIMS: Understanding the identity of odontogenic cells is fundamental to advancing research in tooth development and regeneration. We aim to explore the cellular composition, differentiation pathways, and regulatory networks in human embryonic teeth during the transition from the cap stage to the early bell stage. METHODS: The spatial RNA sequencing and single-nucleus RNA sequencing to human embryonic tooth germs were obtained from four healthy aborted specimens and integrated with public database. The spatial and temporal gene expression patterns, cell distributions, and interactions in tooth germ and surrounding periodontal tissues spanning postconception weeks 12 to 18 were examined and validated by immunohistochemistry. RESULTS: Our analysis identified diverse cell types, including 10 epithelial and nine mesenchymal subpopulations, alongside smooth muscle cells, endothelial cells, macrophages, and Schwann cells. We characterized epithelial and mesenchymal lineages by defining their signature genes, regulatory transcription factors, spatial distributions, and differentiation trajectories, while revealing conserved and distinct features between oral and odontogenic cells. Developmental stage-specific intercellular communications were delineated for epithelial and mesenchymal compartments. Notably, SPP1+ macrophages mediated crosstalk with odontoblasts via SPP1-integrin receptor interactions, whereas Schwann cells contributed to the signalling landscape via SEMA3C/MDK/PDGFC ligands. CONCLUSIONS: This study reveals the cellular heterogeneity present in human embryonic teeth during early development, identifies key genes governing the differentiation of epithelial and mesenchymal cells, and provides valuable transcriptomic resources for investigating human embryonic tooth development. CLINICAL RELEVANCE: Characterizing cells into more precise subgroups will enhance the potential to select optimal cell types for regenerative applications. The characteristic genes in differentiated cells could serve as potential inducers to guide the directed differentiation of stem cells.

Source: International Dental Journal

DOI: 10.1016/j.identj.2025.103920