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Dental cell type atlas reveals new stem and differentiated cell types in mouse and human teeth

ABSTRACT: Reconstruction and engineering of human teeth are the tasks of utmost importance. Here we introduce detailed cellular atlas of the growing and non-growing mouse and human teeth including a condition with caries, which will enhance the field of dental engineering and lead to a better understanding of stem cell niche dynamics enabling tooth growth. We report previously unappreciated cellular complexity of the mouse incisor, including new spatially-restricted stem, progenitor and differentiated populations and compare this model system with the human adult, growing and caries-lesioned teeth. This comparison revealed specific parallelisms in mechanisms of dental growth in humans and mice. Beyond the main mesenchymal and epithelial compartments, we demonstrate a surprising role of the immune system as a mediator of the epithelial-mesenchymal interactions required for proper development. Finally, our results brought new insights into the differentiation of cell lineages producing enamel and dentin, which should be of utmost importance for dental reconstructive engineering.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE146123 | GEO | 2020/02/29

REPOSITORIES: GEO

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Project description:Metabolites are important determinants of disease progression. In this study, we conducted a case-control study to explore permanent teeth caries-related differences in salivary metabolite profiles and related changes in the composition of the oral microbiota in 200 subjects including 100 caries-free individuals and 100 with moderate-to-severe caries with good homogeneity through widely targeted metabolomics and 16S rRNA deep sequencing technologies. We found that: 1) 822 metabolites were detectable in salivary samples from these participants, of which 4-acetamidobutyric acid and adipic acid were respectively enriched in healthy individuals and individuals with caries, exhibited the greatest area under the curve (AUC) values of > 0.970; 2) less diversity was observed in individuals with dental caries relative to caries-free individuals, and significant differences in the dominant taxa were evident between the two groups. For example, the healthy oral microbiome is enriched for Rothia aeria and Neisseria perflava, whereas Prevotella melaninogenica, Streptococcus salivarius, Streptococcus parasanguinis and Prevotella histicola, and Streptococcus mutans were enriched in individuals with caries; 3) Prevotella histicola, Oribacterium asaccharolyticum and Rothia aeria were the top 3 species being required to differentiate caries from caries free population; 4) adipic acid and 4-acetamidobutyric acid derived from microbiota and host-microbiota co-metabolism, respectively. A negative correlation was observed between the microbes enriched in caries individuals (such as Prevotella histicola) and 4-acetamidobutyric acid. Moreover, the upstream regulatory factor ALDH of 4-acetamidobutyric acid is expressed throughout the entire process of tooth development including the differentiation of tooth bud, ameloblasts and odontoblasts. Together, these results suggest that 4-acetamidobutyric acid and adipic acid are important targets for future caries-focused research, offering insight into cariogenic activity or risk assessment in moderate or severe cases.

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Dental cell type atlas reveals new stem and differentiated cell types in mouse and human teeth

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