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<p>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. <i>DLX6-AS1</i><sup>+</sup> DP cells respond to dental epithelial signals and can be isolated from adult dental pulp stem cells (DPSCs). Notably, <i>DLX6-AS1</i><sup>+</sup> 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.</p>

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Spatiotemporal interplay between epithelial and mesenchymal cells drives human dentinogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月14日

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  • Wei Wei,
  • Chuan Wu,
  • Jing Sun,
  • Mengjie Han,
  • Xiuge Gu,
  • Hanzhang Zhou,
  • Xiaoshan Wu,
  • Zongshan Shen,
  • Chunmei Zhang,
  • Jinsong Wang,
  • Lei Hu,
  • Lanrong Luo,
  • Yuanyuan Zhang,
  • Lina Hu,
  • Songlin Wang,
  • Ran Zhang

摘要

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.