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

Florian Hermans; Lara Hemeryck; Celine Bueds; Marc Torres Pereiro; Steffie Hasevoets; Hiroto Kobayashi; Diether Lambrechts; Ivo Lambrichts; Annelies Bronckaers; Hugo Vankelecom

doi:10.1016/j.stemcr.2023.03.011

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

Stem Cell Reports. 2023 May 9;18(5):1166-1181. doi: 10.1016/j.stemcr.2023.03.011. Epub 2023 Apr 20.

Affiliations

¹ 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.
² 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.
³ Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, 3590 Diepenbeek, Belgium.
⁴ Department of Anatomy and Structural Science, Yamagata University Faculty of Medicine, Yamagata, Japan.
⁵ Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
⁶ Department of Morphology, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, 3590 Diepenbeek, Belgium. Electronic address: annelies.bronckaers@uhasselt.be.
⁷ 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. Electronic address: hugo.vankelecom@kuleuven.be.

Abstract

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.

Keywords: ameloblasts; assembloids; dental epithelium; incisors; molars; organoids; single-cell RNA-sequencing; stem cells; tooth development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ameloblasts*
Animals
Biology
Cell Differentiation
Humans
Incisor*
Mice
Molar
Organoids