Tooth dentin, secreted by odontoblasts, constitutes most of the tooth structure and provides support and sensory function. However, dentin defects are common and irreparable once they exceed a critical threshold. Human dentin develops from dental papilla (DP) cells under the guidance of the dental epithelium (DE). Here, we present a human tooth development atlas from initiation to erupted stage using single-cell RNA sequencing and spatial transcriptomics, focusing on epithelial-mesenchymal interactions. This atlas reveals that DE orchestrates DP differentiation in a WNT-NOTCH sequential activation model and identifies the key signaling molecules. DLX6-AS1 + DP cells respond to dental epithelial signals and can be isolated from adult dental pulp stem cells (DPSCs). Notably, DLX6-AS1 + DPSCs successfully generate tubular dentin in an in vivo disease model of dentin defects. This research provides valuable information on human tooth development and establishes a basis for repairing regenerative dental tissue.
Wei et al. (Sat,) studied this question.