A Single-cell Atlas of Human Teeth

Overview

Journal iScience

Publisher Cell Press

Date 2021 May 17

PMID 33997688

Citations 47

Authors

Pierfrancesco Pagella

Laura De Vargas Roditi

Bernd Stadlinger

Andreas E Moor

Thimios A Mitsiadis

Affiliations

Soon will be listed here.

Abstract

Teeth exert fundamental functions related to mastication and speech. Despite their great biomedical importance, an overall picture of their cellular and molecular composition is still missing. In this study, we have mapped the transcriptional landscape of the various cell populations that compose human teeth at single-cell resolution, and we analyzed in deeper detail their stem cell populations and their microenvironment. Our study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar, while their respective microenvironments strongly diverged. Our findings suggest that the microenvironmental specificity is a potential source for functional differences between highly similar stem cells located in the various tooth compartments and open new perspectives toward cell-based dental therapeutic approaches.

Citing Articles

Mutanobactin-D, a Non-Ribosomal Cyclic Lipopeptide, Induces Osteogenic/Odontogenic Differentiation of Human Dental Pulp Stem Cells and Human Bone Marrow Stem Cells.

Nikolic S, Alastra G, Pultar F, Luthy L, Stadlinger B, Carreira E Int J Mol Sci. 2025; 26(3).

PMID: 39940912 PMC: 11817755. DOI: 10.3390/ijms26031144.

Decoding SFRP2 progenitors in sustaining tooth growth at single-cell resolution.

Zhao T, Zhong Q, Sun Z, Yu X, Sun T, An Z Stem Cell Res Ther. 2025; 16(1):58.

PMID: 39920788 PMC: 11806734. DOI: 10.1186/s13287-025-04190-z.

Current Insights into the Roles of LncRNAs and CircRNAs in Pulpitis: A Narrative Review.

Fuchen-Ramos D, Leija-Montoya A, Gonzalez-Ramirez J, Isiordia-Espinoza M, Garcia-Arevalo F, Pitones-Rubio V Int J Mol Sci. 2025; 25(24.

PMID: 39769365 PMC: 11677139. DOI: 10.3390/ijms252413603.

Application of Single-Cell Genomics to Animal Models of Periodontitis and Peri-Implantitis.

Hasuike A, Easter Q, Clark D, Byrd K J Clin Periodontol. 2024; 52(2):268-279.

PMID: 39695834 PMC: 11743042. DOI: 10.1111/jcpe.14093.

Single-cell integration reveals metaplasia in inflammatory gut diseases.

Oliver A, Huang N, Bartolome-Casado R, Li R, Koplev S, Nilsen H Nature. 2024; 635(8039):699-707.

PMID: 39567783 PMC: 11578898. DOI: 10.1038/s41586-024-07571-1.

References

Mitsiadis T, Romeas A, Lendahl U, Sharpe P, Farges J . Notch2 protein distribution in human teeth under normal and pathological conditions. Exp Cell Res. 2003; 282(2):101-9. DOI: 10.1016/s0014-4827(02)00012-5. View

Takimoto A, Kawatsu M, Yoshimoto Y, Kawamoto T, Seiryu M, Takano-Yamamoto T . Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone. Development. 2015; 142(4):787-96. DOI: 10.1242/dev.116228. View

Kaipatur N, Murshed M, McKee M . Matrix Gla protein inhibition of tooth mineralization. J Dent Res. 2008; 87(9):839-44. DOI: 10.1177/154405910808700907. View

Xuan K, Li B, Guo H, Sun W, Kou X, He X . Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth. Sci Transl Med. 2018; 10(455). DOI: 10.1126/scitranslmed.aaf3227. View

Bai Y, Bai Y, Matsuzaka K, Hashimoto S, Kokubu E, Wang X . Formation of bone-like tissue by dental follicle cells co-cultured with dental papilla cells. Cell Tissue Res. 2010; 342(2):221-31. DOI: 10.1007/s00441-010-1046-9. View

Ledesma-Martinez E, Mendoza-Nunez V, Santiago-Osorio E . Mesenchymal Stem Cells Derived from Dental Pulp: A Review. Stem Cells Int. 2016; 2016:4709572. PMC: 4686712. DOI: 10.1155/2016/4709572. View

Mitsiadis T, Rahiotis C . Parallels between tooth development and repair: conserved molecular mechanisms following carious and dental injury. J Dent Res. 2004; 83(12):896-902. DOI: 10.1177/154405910408301202. View

Machado C, Passos S, Campos T, Bernardi L, Vilas-Boas D, Nor J . The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression. Int Endod J. 2015; 49(8):755-63. PMC: 4723291. DOI: 10.1111/iej.12511. View

Krivanek J, Soldatov R, Kastriti M, Chontorotzea T, Herdina A, Petersen J . Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth. Nat Commun. 2020; 11(1):4816. PMC: 7511944. DOI: 10.1038/s41467-020-18512-7. View

10.

Junankar S, Baker L, Roden D, Nair R, Elsworth B, Gallego-Ortega D . ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nat Commun. 2015; 6:6548. DOI: 10.1038/ncomms7548. View

11.

Giri J, Das R, Nylen E, Chinnadurai R, Galipeau J . CCL2 and CXCL12 Derived from Mesenchymal Stromal Cells Cooperatively Polarize IL-10+ Tissue Macrophages to Mitigate Gut Injury. Cell Rep. 2020; 30(6):1923-1934.e4. PMC: 7043065. DOI: 10.1016/j.celrep.2020.01.047. View

12.

Shi S, Gronthos S . Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003; 18(4):696-704. DOI: 10.1359/jbmr.2003.18.4.696. View

13.

Yang H, Adam R, Ge Y, Hua Z, Fuchs E . Epithelial-Mesenchymal Micro-niches Govern Stem Cell Lineage Choices. Cell. 2017; 169(3):483-496.e13. PMC: 5510744. DOI: 10.1016/j.cell.2017.03.038. View

14.

Pagella P, Neto E, Lamghari M, Mitsiadis T . Investigation of orofacial stem cell niches and their innervation through microfluidic devices. Eur Cell Mater. 2015; 29:213-23. DOI: 10.22203/ecm.v029a16. View

15.

Liang T, Zhang H, Xu Q, Wang S, Qin C, Lu Y . Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta. J Dent Res. 2019; 98(8):912-919. PMC: 6616118. DOI: 10.1177/0022034519854029. View

16.

Athanassiou-Papaefthymiou M, Papagerakis P, Papagerakis S . Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament. J Dent Res. 2015; 94(11):1591-600. PMC: 6728676. DOI: 10.1177/0022034515606401. View

17.

Patel D, Morton D, Carey J, Havrda M, Chaudhary J . Inhibitor of differentiation 4 (ID4): From development to cancer. Biochim Biophys Acta. 2014; 1855(1):92-103. PMC: 4312723. DOI: 10.1016/j.bbcan.2014.12.002. View

18.

Nam H, Lee G . Identification of novel epithelial stem cell-like cells in human deciduous dental pulp. Biochem Biophys Res Commun. 2009; 386(1):135-9. DOI: 10.1016/j.bbrc.2009.05.141. View

19.

Otabe K, Muneta T, Kawashima N, Suda H, Tsuji K, Sekiya I . Comparison of Gingiva, Dental Pulp, and Periodontal Ligament Cells From the Standpoint of Mesenchymal Stem Cell Properties. Cell Med. 2016; 4(1):13-21. PMC: 4733865. DOI: 10.3727/215517912X653319. View

20.

Xu M, Horrell J, Snitow M, Cui J, Gochnauer H, Syrett C . WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation. Nat Commun. 2017; 8:15397. PMC: 5467248. DOI: 10.1038/ncomms15397. View