A single cell atlas of human teeth

Pagella, Pierfrancesco; Roditi, Laura De Vargas; Stadlinger, Bernd; Moor, Andreas E.; Mitsiadis, Thimios A.

doi:10.1101/2021.02.19.431962

Cited by 14 publications

(48 citation statements)

References 66 publications

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“…Recently, we performed a thorough single cell RNA sequencing analysis of the human dental pulp and periodontium 37 . We here interrogated this dataset to determine the expression of NOTCH receptors and ligands in dental pulp and periodontal MSCs (Figures 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, Notch3 ‐expressing MSCs are essentially predisposed to differentiate into hard tissue forming cells, contributing to the remodeling and healing of the injured pulp‐dentin complex. In our recent work, we showed that the similarity of MSCs in the dental pulp and the periodontium is counteracted by a great divergence in the composition of their niches 37 . However, previous studies from other laboratories had identified dental pulp and periodontal MSCs as divergent cell populations with distinctive properties 51‐53 .…”

Section: Discussionmentioning

confidence: 97%

“…Relevant differences exist however within the human dental pulp and periodontal tissues in their cellular and molecular composition, 37 which could represent important cues guiding MSCs activation in various physiological or pathological stimuli (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

“…All code is publicly available at: https://github.com/TheMoorLab/Tooth. Single cell RNA sequencing data are described in detail in Reference 37.…”

Section: Methodsmentioning

confidence: 99%

“…NOTCH3 + MSCs also expressed the dental MSCs markers THY1, MYH11, and ACTA2 (Figure 1A). 20,37,39 NOTCH3expressing MSCs were mainly localized around the vessels, where the perivascular niches are formed 21,22 (Figure 1C-G). Double staining against Notch3 and the endothelial cell marker CD31, followed by cell surface analysis, showed that the Notch3-positive MSCs (pericytes) are in direct contact with the CD31-positive endothelial cells (Figure 1H,I).…”

Section: Human Dental Mscs Express Notch3mentioning

confidence: 99%

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Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches

Pagella

Roditi

Stadlinger

et al. 2021

Stem Cells Translational Medicine

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The Notch signaling pathway is a fundamental regulator of cell fate determination in homeostasis and regeneration. In this work, we aimed to determine how Notch signaling mediates the interactions between perivascular stem cells and their niches in human dental mesenchymal tissues, both in homeostatic and regenerative conditions.By single cell RNA sequencing analysis, we showed that perivascular cells across the dental pulp and periodontal human tissues all express NOTCH3, and that these cells are important for the response to traumatic injuries in vivo in a transgenic mouse model. We further showed that the behavior of perivascular NOTCH3-expressing stem cells could be modulated by cellular and molecular cues deriving from their microenvironments. Taken together, the present studies, reinforced by single-cell analysis, reveal the pivotal importance of Notch signaling in the crosstalk between perivascular stem cells and their niches in tissue homeostasis and regeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

“…All code is publicly available at: https://github.com/TheMoorLab/Tooth. Single cell RNA sequencing data are described in detail in Reference 37.…”

Section: Methodsmentioning

confidence: 99%

Section: Human Dental Mscs Express Notch3mentioning

confidence: 99%

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Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches

Pagella

Roditi

Stadlinger

et al. 2021

Stem Cells Translational Medicine

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Diverse stem cells for periodontal tissue formation and regeneration

English

Ono

2022

Genesis

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Summary The periodontium is comprised of multiple units of mineralized and nonmineralized tissues including the cementum on the root surface, the alveolar bone, periodontal ligament (PDL), and the gingiva. PDL contains a variety of cell populations including mesenchymal stem/progenitor cells (MSCs) termed PDLSCs, which contribute to periodontal regeneration. Recent studies utilizing mouse genetic models shed light on the identities of these mesenchymal progenitors in their native environment, particularly regarding how they contribute to homeostasis and repair of the periodontium. The current concept is that mesenchymal progenitors in the PDL are localized to the perivascular niche. Single‐cell RNA sequencing (scRNA‐seq) analyses reveal heterogeneity and cell‐type specific markers of cells in the periodontium, as well as their developmental relationship with precursor cells in the dental follicle. The characteristics of PDLSCs and their diversity in vivo are now beginning to be unraveled thanks to insights from mouse genetic models and scRNA‐seq analyses, which aid to uncover the fundamental properties of stem cells in the human PDL. The new knowledge will be highly important for developing more effective stem cell‐based regenerative therapies to repair periodontal tissues in the future.

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Novel approaches for periodontal tissue engineering

Swanson

Yao

Mishina

2022

Genesis

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Summary The periodontal complex involves the hard and soft tissues which support dentition, comprised of cementum, bone, and the periodontal ligament (PDL). Periodontitis, a prevalent infectious disease of the periodontium, threatens the integrity of these tissues and causes irreversible damage. Periodontal therapy aims to repair and ultimately regenerate these tissues toward preserving native dentition and improving the physiologic integration of dental implants. The PDL contains multipotent stem cells, which have a robust capacity to differentiate into various types of cells to form the PDL, cementum, and alveolar bone. Selection of appropriate growth factors and biomaterial matrices to facilitate periodontal regeneration are critical to recapitulate the physiologic organization and function of the periodontal complex. Herein, we discuss the current state of clinical periodontal regeneration including a review of FDA‐approved growth factors. We will highlight advances in preclinical research toward identifying additional growth factors capable of robust repair and biomaterial matrices to augment regeneration similarly and synergistically, ultimately improving periodontal regeneration's predictability and long‐term efficacy. This review should improve the readers' understanding of the molecular and cellular processes involving periodontal regeneration essential for designing comprehensive therapeutic approaches.

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A single cell atlas of human teeth

Cited by 14 publications

References 66 publications

Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches

Notch Signaling in the Dynamics of Perivascular Stem Cells and their Niches

Diverse stem cells for periodontal tissue formation and regeneration

Novel approaches for periodontal tissue engineering

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