Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, 3590 Diepenbeek, Belgium; Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), 3000 Leuven, Belgium.
Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven (University of Leuven), 3000 Leuven, Belgium.
Stem Cell Reports. 2023 May 9;18(5):1166-1181. doi: 10.1016/j.stemcr.2023.03.011. Epub 2023 Apr 20.
Organoid models provide powerful tools to study tissue biology and development in a dish. Presently, organoids have not yet been developed 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.
类器官模型为研究组织生物学和在培养皿中发育提供了强大的工具。目前，尚未从鼠牙中开发出类器官。在这里，我们从新生后小鼠磨牙和切牙中建立了牙齿类器官 (TO)，这些类器官可以长期扩增，表达牙上皮干细胞 (DESC) 标志物，并以牙齿特异性的方式再现牙上皮的关键特性。TO 在体外向成釉细胞样细胞分化的能力，在与牙间充质（牙髓）干细胞组合的类器官集合体中更为明显。单细胞转录组学支持这种发育潜力，并揭示了在类器官集合体中共同分化为连接上皮细胞和成牙本质细胞/成牙骨质细胞。最后，TO 在体内也能存活并表现出成釉细胞样分化。所开发的类器官模型为研究小鼠牙齿特异性生物学和发育提供了新工具，并获得了更深入的分子和功能见解，最终可能有助于实现未来人类生物牙齿的修复和替代。
