Periodontal tissue stem cells and mesenchymal stem cells in the periodontal ligament

Japanese Dental Science Review, Journal Year: 2022, Volume and Issue: 58, P. 172 - 178

Published: May 17, 2022

Periodontal tissue stem cells, which play a crucial role in maintaining the homeostasis of periodontal tissues, are found ligament (PDL). These cells have long been referred to as mesenchymal stem/stromal (MSCs), and their clinical applications extensively studied. However, PDL not thoroughly investigated, they may be different from MSCs. Recent advances cell biology, such genetic lineage tracing, identification label-retaining single-cell transcriptome analysis, made it possible analyze vivo. In this review, we summarize recent findings on these populations discuss future research directions toward developing regenerative therapy.

Language: Английский

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System‐level analyses of keystone genes required for mammalian tooth development

Journal of Experimental Zoology Part B Molecular and Developmental Evolution, Journal Year: 2020, Volume and Issue: 336(1), P. 7 - 17

Published: Oct. 31, 2020

When a null mutation of gene causes complete developmental arrest, the is typically considered essential for life. Yet, in most cases, mutations have more subtle effects on phenotype. Here we used phenotypic severity as tool to examine system-level dynamics expression. We classify genes required normal development mouse molar into different categories that range from modification Collectively, call these keystone genes. Transcriptome profiling using microarray and RNAseq analyses patterning stage molars show highly elevated expression levels progression tooth development, result reminiscent single-cell organisms. Elevated were also detected developing rat molars, suggesting evolutionary conservation this dynamics. Single-cell reveal even though size domain, measured number cells, main driver organ-level expression, high cell-level transcript abundances. Progression are upregulated within their pathways, which themselves expressed. In contrast, proportion secreted ligands expressed fewer cells than receptors intracellular components. Overall, patterns individual can be different, conserved principles phenotypically defined categories.

Language: Английский

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Single-cell characterization of monolayer cultured human dental pulp stem cells with enhanced differentiation capacity

International Journal of Oral Science, Journal Year: 2021, Volume and Issue: 13(1)

Published: Dec. 1, 2021

Abstract Human dental pulp stem cells (hDPSCs) are easily obtained multipotent cells, however, their potential value in regenerative medicine is hindered by the phenotypic and functional changes after conventional monolayer expansion. Here, we employed single-cell RNA sequencing (scRNA-seq) to comprehensively study transcriptional difference between freshly isolated cultured DPSCs. The cell cluster analysis based on our scRNA-seq data showed that culture resulted a significant cellular composition switch compared However, one subpopulation, characterized as MCAM(+)JAG(+)PDGFRA(−), maintained most characteristics counterparts. Notably, immunofluorescent staining revealed MCAM(+)JAG(+)PDGFRA(−) hDPSCs uniquely located perivascular region of human tissue. Flow-cytometry confirmed proportion remained relatively stable (~2%) regardless physiological senescence or caries. Consistent with annotation data, higher proliferation capacity enhanced vitro multilineage differentiation potentials (osteogenic, chondrogenic adipogenic) counterparts PDGFRA(+) subpopulation. Furthermore, bone tissue formation adipose 4-week subcutaneous implantation nude mice. Taken together, for first time hDPSCs. After expansion, subpopulation resembled fresh which may be beneficial further regeneration applications.

Language: Английский

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Single-Cell Transcriptomic Analysis Reveals Developmental Relationships and Specific Markers of Mouse Periodontium Cellular Subsets

Frontiers in Dental Medicine, Journal Year: 2021, Volume and Issue: 2

Published: Aug. 12, 2021

The periodontium is essential for supporting the functionality of tooth, composed diversity mineralized and non-mineralized tissues such as cementum, periodontal ligament (PDL) alveolar bone. developmentally derived from dental follicle (DF), a fibrous tissue surrounding developing tooth bud. We previously showed through in vivo lineage-tracing experiments that DF contains mesenchymal progenitor cells expressing parathyroid hormone-related protein (PTHrP), which give rise to forming attachment apparatus manner regulated by autocrine signaling PTH/PTHrP receptor. However, developmental relationships between PTHrP+ diverse cell populations constituting remain undefined. Here, we performed single-cell RNA-sequencing (scRNA-seq) analyses integrating two datasets, i.e. PTHrP-mCherry+ at P6 2.3kb Col1a1 promoter-driven GFP+ P25 include descendants cells, cementoblasts, osteoblasts cells. This integrative scRNA-seq analysis revealed heterogeneity their type-specific markers, well with Most importantly, our identified cementoblast-specific metagene discriminate cementoblasts bone osteoblasts, including Pthlh (encoding PTHrP) Tubb3. RNA velocity indicated were directly early stage did not interconvert other types. Further, CellPhoneDB cell-cell communication PTHrP acts on an paracrine manner. Collectively, findings provide insights into lineage hierarchy intercellular interactions level, aiding understand cellular molecular basis formation.

Language: Английский

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Mechanical Stimulation-Induced Calcium Signaling by Piezo1 Channel Activation in Human Odontoblast Reduces Dentin Mineralization

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 24, 2021

Odontoblasts play critical roles in dentin formation and sensory transduction following stimuli on the surface. Exogenous to surface elicit dentinal sensitivity through movement of fluids tubules, resulting cellular deformation. Recently, Piezo1 channels have been implicated mechanosensitive processes, as well Ca 2+ signals odontoblasts. However, human odontoblasts, responses induced by mechanical stimulation, channel expression, its pharmacological properties remain unclear. In present study, we examined functional expression recording direct stimulation-induced signaling matrix protein 1 (DMP-1)-, nestin-, sialophosphoprotein (DSPP)-immunopositive Mechanical stimulation odontoblasts transiently increased intracellular free calcium concentration ([Ca ] i ). Application repeated resulted transient [Ca increases, but did not show any desensitizing effects increases. We also observed a increase neighboring stimulated cells during showing decrease with an increasing distance from mechanically cells. Yoda1 . This was inhibited application Gd 3+ Dooku1, respectively. or Dooku1. When were knocked down gene silencing short hairpin RNA (shRNA), almost completely abolished. knockdown attenuated number Piezo1-immunopositive immunofluorescence analysis, while no Piezo2-immunopositive Alizarin red staining distinctly showed that activation significantly suppressed mineralization, shRNA-mediated enhanced mineralization. These results suggest predominantly activates via opening, rather than Piezo2 channels, signal establishes intercellular odontoblast-odontoblast communication. addition, participates reduction dentinogenesis. Thus, pathway mediated could contribute function two ways: (1) generating (2) suppressing physiological/reactional dentinogenesis, deformation hydrodynamic forces inside tubules.

Language: Английский

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