Organoids from mouse molar and incisor as new tools to study tooth-specific biology and development

Organoid models provide powerful tools to study tissue biology and development in a dish. Presently, organoids have not yet been devel-oped from mouse tooth. Here, we established tooth organoids (TOs) from early-postnatal mouse molar and incisor, which are long-term expandable, express dental epithelium stem cell (DESC) markers, and recapitulate key properties of the dental epithelium in a tooth-type -specific manner. TOs display in vitro differentiation capacity toward ameloblast-resembling cells, even more pronounced in assembloids in which dental mesenchymal (pulp) stem cells are combined with the organoid DESCs. Single-cell transcriptomics supports this developmental potential and reveals co-differentiation into junctional epithelium-and odontoblast-/cementoblast-like cells in the assembloids. Finally, TOs survive and show ameloblast-resembling differentiation also in vivo. The developed organoid models provide new tools to study mouse tooth-type-specific biology and development and gain deeper molecular and functional insights that may eventually help to achieve future human biological tooth repair and replacement.

Automated summary

Organoid models have been successfully established to study tissue biology and development in a dish. In this study, tooth organoids (TOs) were developed from mouse molar and incisor, which express dental epithelium stem cell markers and recapitulate key properties of dental epithelium. These TOs can differentiate into ameloblast-resembling cells and co-differentiate into different cell types in the presence of dental mesenchymal stem cells. Furthermore, the TOs can also survive and differentiate in vivo. These organoid models provide new tools to study mouse tooth biology and development and may have implications for future human tooth repair and replacement.