Project description:Teeth exert fundamental functions related to mastication and speech. Despite their big biomedical interest, an overall picture of their cellular and molecular composition is still lacking. We here mapped the transcriptional landscape of the various stem cell populations and their microenvironments in human teeth at single-cell resolution. Our analysis identified significant cellular heterogeneity between the various dental tissues. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar in vivo, and that their distinctive behavior was due to substantial differences between their microenvironments. Furthermore, we showed that the evolutionarily conserved Notch signaling pathway is important for the interactions between dental stem cells and the diverse cell types composing their niches. Our findings reveal that the microenvironmental specificity is responsible for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards dental cell-based therapeutic approaches.
Project description:Teeth exert fundamental functions related to mastication and speech. Despite their big biomedical interest, an overall picture of their cellular and molecular composition is still lacking. We here mapped the transcriptional landscape of the various stem cell populations and their microenvironments in human teeth at single-cell resolution. Our analysis identified significant cellular heterogeneity between the various dental tissues. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar in vivo, and that their distinctive behavior was due to substantial differences between their microenvironments. Furthermore, we showed that the evolutionarily conserved Notch signaling pathway is important for the interactions between dental stem cells and the diverse cell types composing their niches. Our findings reveal that the microenvironmental specificity is responsible for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards dental cell-based therapeutic approaches.
Project description:Reconstruction and engineering of human teeth are the tasks of utmost importance. Here we introduce detailed cellular atlas of the growing and non-growing mouse and human teeth including a condition with caries, which will enhance the field of dental engineering and lead to a better understanding of stem cell niche dynamics enabling tooth growth. We report previously unappreciated cellular complexity of the mouse incisor, including new spatially-restricted stem, progenitor and differentiated populations and compare this model system with the human adult, growing and caries-lesioned teeth. This comparison revealed specific parallelisms in mechanisms of dental growth in humans and mice. Beyond the main mesenchymal and epithelial compartments, we demonstrate a surprising role of the immune system as a mediator of the epithelial-mesenchymal interactions required for proper development. Finally, our results brought new insights into the differentiation of cell lineages producing enamel and dentin, which should be of utmost importance for dental reconstructive engineering.
Project description:Tooth enamel secreted by ameloblasts is the hardest material in the human body, acting as a shield protecting the teeth. However, enamel is gradually damaged or partially lost in over 90% of adults and cannot be regenerated due to a lack of ameloblasts in erupted teeth. Here we use sci-RNA-seq to establish a spatiotemporal single cell atlas for the developing human tooth and identify regulatory mechanisms controlling the differentiation process of human ameloblasts. We reveal key signaling pathways involved between the support cells and ameloblasts during fetal development and recapitulate those findings in a novel human ameloblast in vitro differentiation from iPSCs. We furthermore develop a mineralizing enamel organ-like 3D organoid system. These studies pave the way for future regenerative dentistry and therapies toward genetic diseases affecting enamel formation.