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Frontiers in Cell and Developmental... 2021Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These...
Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 . Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells.
PubMed: 34901015
DOI: 10.3389/fcell.2021.769193 -
Cell and Tissue Research Feb 2021The dental pulp, a non-mineralized connective tissue uniquely encased within the cavity of the tooth, provides a niche for diverse arrays of dental mesenchymal stem... (Review)
Review
The dental pulp, a non-mineralized connective tissue uniquely encased within the cavity of the tooth, provides a niche for diverse arrays of dental mesenchymal stem cells. Stem cells in the dental pulp, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs) and stem cells from apical papilla (SCAPs), have been isolated from human tissues with an emphasis on their potential application to regenerative therapies. Recent studies utilizing mouse genetic models shed light on the identities of these mesenchymal progenitor cells derived from neural crest cells (NCCs) in their native conditions, particularly regarding how they contribute to homeostasis and repair of the dental tissue. The current concept is that at least two distinct niches for stem cells exist in the dental pulp, e.g., the perivascular niche and the perineural niche. The precise identities of these stem cells and their niches are now beginning to be unraveled thanks to sophisticated mouse genetic models, which lead to better understanding of the fundamental properties of stem cells in the dental pulp and the apical papilla in humans. The new knowledge will be highly instrumental for developing more effective stem cell-based regenerative therapies to repair teeth in the future.
Topics: Animals; Biomarkers; Dental Papilla; Dental Pulp; Mice; Models, Genetic; Stem Cell Niche; Stem Cells
PubMed: 32803323
DOI: 10.1007/s00441-020-03271-0 -
Head and Neck Pathology Jun 2022Primordial odontogenic tumor (POT) is a rare, mixed odontogenic neoplasm composed of spindled and stellate-shaped cells in myxoid stroma resembling dental papilla,...
Primordial odontogenic tumor (POT) is a rare, mixed odontogenic neoplasm composed of spindled and stellate-shaped cells in myxoid stroma resembling dental papilla, surfaced by cuboidal-to-columnar odontogenic epithelium. Most POTs present in the posterior mandible as a well-demarcated radiolucency associated with a developing tooth in children and adolescents. POT is treated conservatively with no recurrences documented to-date. To describe the clinicopathological features of a recurrent POT. A 19-year-old female presented with an asymptomatic swelling, and panoramic radiograph revealed a multiloculated radiolucency in the mandibular body and ramus, with buccal and lingual perforation. The tumor was composed of plump spindle and stellate cells in a delicately collagenous and myxoid stroma, surfaced by columnar epithelial cells with reverse nuclear polarization. There was extensive epithelial proliferation forming invaginations within the tumor mass and organoid/enamel organ-like structures with enameloid-like deposits, dentinoid, and dystrophic calcifications. This was similar to the POT that had been excised four years prior from the same location. The patient underwent hemi-mandibulectomy and currently is free of disease at a thirteen-month follow-up. This report describes the first recurrent POT exhibiting extensive epithelial proliferation.
Topics: Adolescent; Adult; Child; Epithelium; Female; Humans; Mandible; Odontogenic Tumors; Young Adult
PubMed: 34224080
DOI: 10.1007/s12105-021-01354-0 -
Cellular and Molecular Life Sciences :... Apr 2022Traumatic spinal cord injury is an overwhelming condition that strongly and suddenly impacts the patient's life and her/his entourage. There are currently no predictable...
Traumatic spinal cord injury is an overwhelming condition that strongly and suddenly impacts the patient's life and her/his entourage. There are currently no predictable treatments to repair the spinal cord, while many strategies are proposed and evaluated by researchers throughout the world. One of the most promising avenues is the transplantation of stem cells, although its therapeutic efficiency is limited by several factors, among which cell survival at the lesion site. In our previous study, we showed that the implantation of a human dental apical papilla, residence of stem cells of the apical papilla (SCAP), supported functional recovery in a rat model of spinal cord hemisection. In this study, we employed protein multiplex, immunohistochemistry, cytokine arrays, RT- qPCR, and RNAseq technology to decipher the mechanism by which the dental papilla promotes repair of the injured spinal cord. We found that the apical papilla reduced inflammation at the lesion site, had a neuroprotective effect on motoneurons, and increased the apoptosis of activated macrophages/ microglia. This therapeutic effect is likely driven by the secretome of the implanted papilla since it is known to secrete an entourage of immunomodulatory or pro-angiogenic factors. Therefore, we hypothesize that the secreted molecules were mainly produced by SCAP, and that by anchoring and protecting them, the human papilla provides a protective niche ensuring that SCAP could exert their therapeutic actions. Therapeutic abilities of the papilla were demonstrated in the scope of spinal cord injury but could very well be beneficial to other types of tissue.
Topics: Animals; Female; Humans; Microglia; Rats; Spinal Cord; Spinal Cord Injuries; Spinal Cord Regeneration; Stem Cells
PubMed: 35445984
DOI: 10.1007/s00018-022-04210-8 -
Current Stem Cell Research & Therapy 2018Mesenchymal stem cells (MSCs) in teeth have been exploited as vital seed cells for stem cell-based dental medicine. To date, several mesenchymal stem cell populations... (Review)
Review
BACKGROUND
Mesenchymal stem cells (MSCs) in teeth have been exploited as vital seed cells for stem cell-based dental medicine. To date, several mesenchymal stem cell populations originated from odontogenic tissue have been isolated and characterized by their expression of MSC surface markers and capacity of multi-lineage differentiation, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP) and so on. However, their identity in vivo remains elusive, which hinders further understanding of their application in stem cell-based tooth regeneration. Label retaining and lineage tracing analyses, which serve as gold standards for identification of stem cells in vivo, provide feasibility for identifying MSCs in teeth.
OBJECTIVES
In this review, we will discuss the issues of MSCs, including the origin and identification of both odontogenic and non-odontogenic MSCs, and address the role of nerve-derived Sonic hedgehog (Shh) in the regulation of MSCs in the neurovascular bundle (NVB).
CONCLUSION
Based on label retaining and lineage tracing analyses, latest studies have found new populations of non-odontogenic MSCs in teeth, periarterial-derived and glial-derived, regulated by the Shh derived from nerves in the NVB, which provides a new hope for tooth regeneration.
Topics: Animals; Cell Differentiation; Dental Papilla; Dental Pulp; Epigenesis, Genetic; Humans; Mesenchymal Stem Cells; Odontogenesis; Periodontal Ligament; Signal Transduction; Tissue Engineering; Tooth
PubMed: 28901252
DOI: 10.2174/1574888X12666170913150403 -
The Journal of Craniofacial Surgery Sep 2016Ameloblastic fibro-odontoma (AFO) is a mixed odontogenic tumor that presents epithelial and mesenchymal components. Ameloblastic fibro-odontoma is generally diagnosed...
Ameloblastic fibro-odontoma (AFO) is a mixed odontogenic tumor that presents epithelial and mesenchymal components. Ameloblastic fibro-odontoma is generally diagnosed between the first and second decades of life and normally shows a slow clinical growth in the posterior portion of the maxilla or mandible, being mostly associated with 1 or more impacted teeth. Radiographic features of AFO show a radiolucent well-defined, uni, or multilocular defect due to containing variable amounts of calcified material. The enucleation of the tumor is the usual conduct and should be followed up for a long period of time. Here, the authors report the case of 17-year-old male patient who presented an extensive AFO on the right posterior side of the mandible. The panoramic radiograph and the tomographic examination revealed a multilocular radiolucent lesion with impacted teeth. Histological examination revealed connective tissue resembling the dental papilla along with epithelial strands or islands, as well as dental hard tissue such enamel and dentin. Enucleation and curettage was performed and led to good outcome. There was no recurrence after an 8-year follow-up, and oral rehabilitation was performed with dental implants.
Topics: Adolescent; Biopsy; Humans; Male; Mandible; Mandibular Neoplasms; Mandibular Osteotomy; Odontoma; Radiography, Panoramic; Tomography, X-Ray Computed
PubMed: 27428924
DOI: 10.1097/SCS.0000000000002869 -
Frontiers in Bioengineering and... 2022Stem cells (SCs) research has experienced exponential growth in recent years. SC-based treatments can enhance the lives of people suffering from cardiac ischemia,... (Review)
Review
Stem cells (SCs) research has experienced exponential growth in recent years. SC-based treatments can enhance the lives of people suffering from cardiac ischemia, Alzheimer's disease, and regenerative drug conditions, like bone or loss of teeth. Numerous kinds of progenitor/SCs have been hypothesized to depend on their potential to regain and/or heal wounded tissue and partly recover organ function. Growing data suggest that SCs (SCs) are concentrated in functions and that particular tissues have more SCs. Dental tissues, in particular, are considered a significant cause of mesenchymal stem cells (MSCs) cells appropriate for tissue regeneration uses. Tissue regeneration and SCs biology have particular attention in dentistry because they may give a novel method for creating clinical material and/or tissue redevelopment. Dental pulp, dental papilla, periodontal ligament, and dental follicle contain mesenchymal SCs. Such SCs, which must be identified and cultivated in specific tissue culture environments, may be used in tissue engineering applications such as tooth tissue, nerve regeneration, and bone redevelopment. A new cause of SCs, induced pluripotent SCs, was successfully made from human somatic cells, enabling the generation of the patient and disease-specific SCs. The dental SC's (DSCs) multipotency, rapid proliferation rate, and accessibility make it an ideal basis of MSC for tissue redevelopment. This article discusses current advances in tooth SC investigation and its possible application in tissue redevelopment.
PubMed: 35497335
DOI: 10.3389/fbioe.2022.855396 -
Science Bulletin Jun 2022The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood. We report a cell lineage and atlas of developing mouse teeth. We...
The spatiotemporal relationships in high-resolution during odontogenesis remain poorly understood. We report a cell lineage and atlas of developing mouse teeth. We performed a large-scale (92,688 cells) single cell RNA sequencing, tracing the cell trajectories during odontogenesis from embryonic days 10.5 to 16.5. Combined with an assay for transposase-accessible chromatin with high-throughput sequencing, our results suggest that mesenchymal cells show the specific transcriptome profiles to distinguish the tooth types. Subsequently, we identified key gene regulatory networks in teeth and bone formation and uncovered spatiotemporal patterns of odontogenic mesenchymal cells. CD24 and Plac8 cells from the mesenchyme at the bell stage were distributed in the upper half and preodontoblast layer of the dental papilla, respectively, which could individually induce nonodontogenic epithelia to form tooth-like structures. Specifically, the Plac8 tissue we discovered is the smallest piece with the most homogenous cells that could induce tooth regeneration to date. Our work reveals previously unknown heterogeneity and spatiotemporal patterns of tooth germs that may lead to tooth regeneration for regenerative dentistry.
Topics: Mice; Animals; Odontogenesis; Tooth; Tooth Germ; Mesenchymal Stem Cells; Epithelium
PubMed: 36545982
DOI: 10.1016/j.scib.2022.03.012 -
Acta Odontologica Scandinavica May 2022To assess the efficacy and safety of hyaluronic acid (HA) injections to restore the lost interproximal papilla. (Review)
Review
OBJECTIVES
To assess the efficacy and safety of hyaluronic acid (HA) injections to restore the lost interproximal papilla.
MATERIALS AND METHODS
A systematic literature search was conducted in PubMed/MEDLINE, Scopus and Cochrane electronic databases with no time restriction up to September 2021. Any clinical study evaluating HA injection into the interproximal papilla loss Class I and II according to Norland & Tarnow, were included based on the following PICO questions (1) Are HA injections effective for the reconstruction of the interproximal papilla loss? (2) What are the side/adverse effects of using HA for the reconstruction of interproximal papilla loss? The risk of bias assessment was performed using the Cochrane Collaboration's the Newcastle Ottawa and Joanna Briggs institute tools.
RESULTS
A total of 1497 titles were retrieved. From these, eleven were included and underwent full data extraction. However, due to heterogeneity in the data among the included articles, a meta-analysis could not be performed. Three articles reported no-differences in term of papilla tip to contact point distance or the papilla fill reduction. Finally, five studies showed a reduction in the black triangle with a percentage range between 19 and 47%.
CONCLUSION
The non-surgical use of HA injection seems to have a positive effect on the re-establishment of interproximal papilla lost. However post-operative complications might develop.
Topics: Esthetics, Dental; Gingiva; Humans; Hyaluronic Acid; Injections
PubMed: 34855562
DOI: 10.1080/00016357.2021.2007282 -
Stem Cells and Development Jul 2015Although regenerative endodontic procedures have yielded an impressive body of favorable outcomes, the treatment of necrotic immature permanent teeth in particular... (Review)
Review
Although regenerative endodontic procedures have yielded an impressive body of favorable outcomes, the treatment of necrotic immature permanent teeth in particular remains to be a challenge. Recent advances in dental stem cell (DSC) research have gained increasing insight in their regenerative potential and prospective use in the formation of viable dental tissues. Numerous studies have already reported successful dental pulp regeneration following application of dental pulp stem cells, stem cells from the apical papilla, or dental follicle precursor cells in different in vivo models. Next to responsive cells, dental tissue engineering also requires the support of an appropriate scaffold material, ranging from naturally occurring polymers to treated dentin matrix components. However, the routine use and banking of DSCs still holds some major challenges, such as culture-associated differences, patient-related variability, and the effects of culture medium additives. Only in-depth evaluation of these problems and the implementation of standardized models and protocols will effectively lead to better alternatives for patients who no longer benefit from current treatment protocols.
Topics: Dental Papilla; Dental Pulp; Dental Sac; Endodontics; Guided Tissue Regeneration; Humans; Neovascularization, Physiologic; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 25869156
DOI: 10.1089/scd.2014.0510