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      A single-cell atlas of human teeth

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          Summary

          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.

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          Highlights

          • Dental atlas of the pulp and periodontal tissues of human teeth

          • Identification of three common MSC subclusters between dental pulp and periodontium

          • Dental pulp and periodontal MSCs are similar, and their niches diverge

          Abstract

          Cell Biology; Stem Cells Research; Omics; Transcriptomics

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          Most cited references77

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          Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

          The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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            UMAP: Uniform Manifold Approximation and Projection

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              Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo.

              Dentinal repair in the postnatal organism occurs through the activity of specialized cells, odontoblasts, that are thought to be maintained by an as yet undefined precursor population associated with pulp tissue. In this study, we isolated a clonogenic, rapidly proliferative population of cells from adult human dental pulp. These DPSCs were then compared with human bone marrow stromal cells (BMSCs), known precursors of osteoblasts. Although they share a similar immunophenotype in vitro, functional studies showed that DPSCs produced only sporadic, but densely calcified nodules, and did not form adipocytes, whereas BMSCs routinely calcified throughout the adherent cell layer with clusters of lipid-laden adipocytes. When DPSCs were transplanted into immunocompromised mice, they generated a dentin-like structure lined with human odontoblast-like cells that surrounded a pulp-like interstitial tissue. In contrast, BMSCs formed lamellar bone containing osteocytes and surface-lining osteoblasts, surrounding a fibrous vascular tissue with active hematopoiesis and adipocytes. This study isolates postnatal human DPSCs that have the ability to form a dentin/pulp-like complex.
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                Author and article information

                Contributors
                Journal
                iScience
                iScience
                iScience
                Elsevier
                2589-0042
                23 April 2021
                21 May 2021
                23 April 2021
                : 24
                : 5
                : 102405
                Affiliations
                [1 ]Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, Center of Dental Medicine, University of Zurich, Plattenstrasse 11, 8032 Zurich, Switzerland
                [2 ]Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
                [3 ]Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, Zurich, Switzerland
                Author notes
                []Corresponding author andreas.moor@ 123456bsse.ethz.ch
                [∗∗ ]Corresponding author thimios.mitsiadis@ 123456zzm.uzh.ch
                [4]

                Present address: Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, 4058 Basel, Switzerland

                [5]

                These authors contributed equally

                [6]

                Lead contact

                Article
                S2589-0042(21)00373-4 102405
                10.1016/j.isci.2021.102405
                8099559
                33997688
                8021fe56-4800-4ffe-b6ae-f6da31f02522
                © 2021 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 24 February 2021
                : 29 March 2021
                : 6 April 2021
                Categories
                Article

                cell biology,stem cells research,omics,transcriptomics
                cell biology, stem cells research, omics, transcriptomics

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