器官样模型为研究组织生物学和发育提供了强大的工具。目前，还没有从老鼠牙齿中开发出器官样。在这里，我们从早期的青年期小鼠臼齿和切牙中建立了牙齿器官样（TOs），TOs可以长期扩增，表达牙齿上皮干细胞（DESC）标记，并以特定于牙齿类型的方式重现牙齿上皮的关键特性。TOs在体外展示向类似于牙珐琅质细胞的分化能力，在与器官样DESCs结合的组成体中更为明显，在其中牙髓干细胞与器官样DESCs相结合。单细胞转录组支持这种发育潜力，并揭示了在组成体中共同分化成交界上皮样和牙本质细胞/牙骨质细胞样细胞。最后， TOs也可以在体内存活并展示类似于牙珐琅质细胞的分化。开发的器官样模型提供了研究老鼠牙齿特异性生物学和发育的新工具，并获得更深层次的分子和功能洞察，这可能最终有助于实现未来的人类生物牙齿修复和更换。版权所有©2023作者。Elsevier Inc.保留所有权利。

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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.