Abstract

Enamel is secreted by ameloblasts derived from tooth epithelial stem cells (SCs). Humans cannot repair or regenerate enamel, due to early loss of tooth epithelial SCs. Contrarily in the mouse incisors, epithelial SCs are maintained throughout life and endlessly generate ameloblasts, and thus enamel. Here we isolated Sox2-GFP+ tooth epithelial SCs which generated highly cellular spheres following a novel in vitro strategy. This system enabled analysis of SC regulation by various signaling molecules, and supported the stimulatory and inhibitory roles of Shh and Bmp, respectively; providing better insight into the heterogeneity of the SCs. Further, we generated a novel mouse reporter, Enamelin-tdTomato for identification of ameloblasts in live tissues and cells, and used it to demonstrate presence of ameloblasts in the new 3D co-culture system of dental SCs. Collectively, our results provide means of generating 3D tooth epithelium from adult SCs which can be utilized toward future generation of enamel.

Details

Title
Novel strategies for expansion of tooth epithelial stem cells and ameloblast generation
Author
Binder, Martin 1 ; Biggs, Leah C 2   VIAFID ORCID Logo  ; Kronenberg, Mark S 3 ; Schneider, Pascal 4   VIAFID ORCID Logo  ; Thesleff Irma 1 ; Balic Anamaria 1 

1  University of Helsinki, Research Program in Developmental Biology, Institute of Biotechnology, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
2  University of Helsinki, Helsinki Institute of Life Science, Biomedicum Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); University of Helsinki, Wihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); University of Helsinki, Stem Cells and Metabolism Research Program, Faculty of Medicine, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071) 
3  Center for Regenerative Medicine and Skeletal Development, School of Dental Medicine, UConn Health, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394); Department of Reconstructive Sciences, School of Dental Medicine, UConn Health, Farmington, USA (GRID:grid.208078.5) (ISNI:0000000419370394) 
4  University of Lausanne, Department of Biochemistry, Epalinges, Switzerland (GRID:grid.9851.5) (ISNI:0000 0001 2165 4204) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-60708-w
ProQuest document ID
2378829518
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.