Volumetric imaging and single-cell RNAseq atlases identify cellular mechanisms of human dental pulp response during tooth decay progression

Dental decay induces dental pulp's responses, which are still unclear. Firstly, we performed a complete volumetric imaging. Samples from healthy and diseased teeth were collected, processed into thick sections, transparized, immunolabeled, and imaged. Secondly, we performed single-cell RNA sequencing analyses of human dental pulps across health and various stages of the disease. We generated an extensive imaging atlas of the pulp's neurovascular systems. We also identified distinct cell population and subpopulations showing the cellular heterogeneity, including large populations of fibroblasts, mesenchymal progenitor and endothelial cells. These results provide a basis for understanding dental tissue response to injury, potentially driving a paradigm shift in patient management. Furthermore, the human tooth seems to be a promising model for investigating systemic diseases and therapeutic responses.