DPSCs Transfer Mitochondria via TNTs to Drive Hypoxic Angiogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE338573 | GEO | 2026/07/15
REPOSITORIES: GEO
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Project description:Pluripotent stem cells can switch their unique metabolic requirements to facilitate cellular changes but it is not clear if adult stem cells utilize metabolism in a similar manner. Here we studied the metabolism of a human adult stem cell: dental pulp stem cells (DPSCs). The dental pulp from third molars of a diverse patient group was surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteogenic and adipogenic lineages. Through RNA seq analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-β) pathway and the proteins associated with muscle contraction are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs. This metabolic signature can be used to predict the onset of replicative senescence phenotypes. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging.
2018-12-18 | GSE123973 | GEO
Project description:Tooth pulp contains various types of cells such as endothelial cells, neurons, fibroblasts, osteoblasts, osteoclasts, and odontoblasts. As well as cells that are called "postnatal dental pulp stem cells" (DPSCs). Also, four more types of dental MSC-like populations were identified and characterized: stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from the apical papilla (SCAP) and population of dental follicle-derived progenitor cells called "dental follicle progenitor cells" (DFPCs). Most of them might be used in wide range of biomedical applications. Nevertheless, they have systematic differences in their physiology, e.g. differences in proliferative and differentiation potential. These differences are not clearly defined on molecular level yet; therefore, we performed proteomics comparison of DPSCs and PDLSCs in control and osteogenic differentiation. Donor matched DPSCs and PDLSCs were isolated from two donors by standard protocol. Then, DPSCs and PDLSCs at passage 3 were seeded into 90 mm Petri dishes (Eppendorf) and cultured in standard conditions with DMEM (Gibco) supplemented with 15% fetal bovine serum (FBS), 37°C, 5% CO2. When cells reached 90-100% confluency, the medium was changed to osteogenic medium (DMEM supplemented with 10% FBS, 2 mM L-glutamine, 1% penicillin/streptomycin (HyClone), 50 mg/ml ascorbic acid (Sigma Aldrich), 0.1 mM dexamethasone (Sigma Aldrich) and 10 mM b–glycerophosphate (Sigma Aldrich).
2021-11-25 | PXD027719 | Pride
Project description:Tissue resident adult stem cells are known to participate in tissue regeneration and repair that follows cell turnover, or injury. It has been well established that aging impedes the regeneration capabilities at the cellular level, but it is not clear if the different onset of stem cell aging between individuals can be predicted or prevented at an earlier stage. Here we studied the dental pulp stem cells (DPSCs), a population of adult stem cells that is known to participate in the repair of an injured tooth, and its properties can be affected by aging. The dental pulp from third molars of a diverse patient group were surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteo/odontogenic and adipogenic lineages. Through RNA seq and qPCR analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput transcriptomic and proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-β) pathway and the cytoskeletal proteins are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs, prior to manifestation of senescence phenotypes. This metabolic signature therefore can be used to predict the onset of replicative senescence. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging.
2019-11-12 | PXD011962 | Pride
Project description:Objectives: Dental pulp stem cells are crucial in immune response regulation. However, sub-clusters of these cells involved in deep caries progression remain unidentified. This study explores the role of Intercellular adhesion molecule 1-positive dental pulp stem cells (ICAM1+DPSCs) within the immune microenvironment of dental pulp tissue affected by deep caries, aiming to establish a theoretical foundation and novel strategies for its prevention and treatment.Methods: Use flow cytometry to sort ICAM1+ DPSCs and ICAM1- DPSCs for RNA-seq.
2026-01-01 | GSE282493 | GEO
Project description:Using the HumanMethylation450 Beadchip, whole genomes of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs) were compared.The DNA methylation profiles were obtained across approximately 485,512 CpGs in human odontogenic stem cells samples. Samples included DPSCs, DFPCs and PDLSCs from each 4 (12 in total) human individuals.
2021-04-10 | GSE112933 | GEO
Project description:Background: Oral submucous fibrosis (OSF) is a precancerous lesion characterized by fibrous tissue deposition, the incidence of which correlates positively with the frequency of betel nut chewing. Prolonged betel nut chewing can damage the integrity of the oral mucosal epithelium, leading to chronic inflammation and local immunological derangement. However, currently, the underlying cellular events driving fibrogenesis and dysfunction are incompletely understood, such that OSF has few treatment options with limited therapeutic effectiveness. Dental pulp stem cells (DPSCs) have been recognized for their anti-inflammatory and anti-fibrosis capabilities, making them promising candidates to treat a range of immune, inflammatory, and fibrotic diseases. However, the application of DPSCs in OSF is inconclusive. Therefore, this study aimed to explore the pathogenic mechanism of OSF and, based on this, to explore new treatment options. Methods: A human cell atlas of oral mucosal tissues was compiled using single-cell RNA sequencing to delve into the underlying mechanisms. Epithelial cells were reclustered to observe the heterogeneity of OSF epithelial cells and their communication with immune cells. The results were validated in vitro, in clinicopathological sections, and in animal models. In vivo, the therapeutic effect and mechanism of DPSCs were characterized by histological staining, immunohistochemical staining, scanning electron microscopy, and atomic force microscopy. Results: A unique epithelial cell population, Epi1.2, with proinflammatory and profibrotic functions, was predominantly found in OSF. Epi1.2 cells also induced the fibrotic process in fibroblasts by interacting with T cells through receptor-ligand crosstalk between macrophage migration inhibitory factor (MIF)-CD74 and C-X-C motif chemokine receptor 4 (CXCR4). Furthermore, we developed OSF animal models and simulated the clinical local injection process in the rat buccal mucosa using DPSCs to assess their therapeutic impact and mechanism. In the OSF rat model, DPSCs demonstrated superior therapeutic effects compared with the positive control (glucocorticoids), including reducing collagen deposition and promoting blood vessel regeneration. DPSCs mediated immune homeostasis primarily by regulating the numbers of KRT19+MIF+ epithelial cells and via epithelial-stromal crosstalk. Conclusions: Given the current ambiguity surrounding the cause of OSF and the limited treatment options available, our study reveals that epithelial cells and their crosstalk with T cells play an important role in the mechanism of OSF and suggests the therapeutic promise of DPSCs.
2024-05-17 | GSE262446 | GEO
Project description:As a key factor for cell pluripotent and self-renewing phenotypes, SOX2 has attracted scientists’ attention gradually in recent years. However, its exact effects in dental pulp stem cells (DPSCs) are still unclear. In this study, we mainly investigated whether SOX2 could affect some biological functions of DPSCs.
2015-09-30 | GSE73548 | GEO
Project description:Tooth decay, also known as dental caries, is a prevalent oral health problem that significantly reduces an individual's quality of life; however, it can be effectively managed through restorative treatments. The condition primarily affects the enamel and dentin structures and can be treated before it progresses to the pulp chamber. Even in cases where the caries does not reach the pulp, microbial products from the lesion can still penetrate the pulp chamber, potentially inducing stress on pulp cells, including dental pulp stem cells (DPSCs). Even in the absence of direct pulpal exposure, microbial by-products originating from carious lesions may diffuse through dentinal tubules, potentially exerting stress on pulpal cells, including dental pulp stem cells (DPSCs). In this study, we performed a comparative analysis of the biological and proteomic profiles of DPSCs isolated from carious teeth that had not reached the pulp and those isolated from healthy teeth. In this study, we conducted a comparative analysis of the biological and proteomic profiles of dental pulp stem cells (DPSCs) isolated from clinically asymptomatic teeth with deep dentinal caries that had not reached the pulp and those isolated from healthy teeth. After evaluation of biological mechanisms such as senescence and apoptosis, we examined both the whole-cell proteome and secretome of these DPSCs by conducting a shotgun proteomics approach. Our findings indicate that the DPSC population isolated from decayed teeth exhibited a significantly higher proportion of senescent cells compared to the control group. Proteomic analysis further revealed that DPSCs from decayed teeth activated specific signaling pathways in response to microbial products, manifesting an inflammatory profile. Additionally, we observed an upregulation in the expression of proteins associated with extracellular matrix (ECM) remodeling and components of the senescence-associated secretory phenotype (SASP), both of which are hallmarks of the senescence process. This study highlights that even in the absence of direct pulp involvement, microbial stress resulting from caries can impact DPSCs within the pulp. The study reveals that DPSCs can be affected by microbial signals from carious lesions, even when the pulp appears clinically intact. The activation of senescence and inflammatory mechanisms in these affected cells may have deleterious effects on other critical tissues within the organism. Consequently, restorative treatments should consider targeting not only the decayed tissue but also the senescent cells within the pulp that may have been affected by the microbial stress induced by caries.
2026-04-27 | PXD064565 | Pride
Project description:Regenerative vascular medicine has received considerable attention due to recent advancements suggesting that the conversion of somatic cells into endothelial cells offers a promising approach to address diseases related to abnormal vessel growth and endothelial cell dysfunction. The therapeutic potential of this method lies in the ability of DPSCs, upon exposure to DMP1, to differentiate into endothelial cells and support the formation of new blood vessels. Despite this progress, there is a need for a comprehensive understanding of the expression profile during endothelial differentiation. Gene ontology and genome functional enrichment analyses have provided insight into the differentiation of ECs from DMP1-treated DPSCs in conjunction with HUVEC-ECM, as compared to positive HUVECs. Our RNA sequence data underscores the striking similarity in gene expression patterns between the sorted DPSCs treated with DMP1 and the positive control HUVECs. These findings could contribute to a comprehensive understanding of the molecular mechanisms underlying the impact of DMP1 treatment on DPSCs, particularly in the context of guiding endothelial cells.
2024-05-07 | GSE266875 | GEO
Project description:To evaluate the miRNA and mRNA expression profiles (miRNOME) we identified miRNAs during in vitro osteogenic differentiation of human dental pulp stem cells (DPSC). The DPSCs were cultured in the DMEM + beta-glycerol phosphate, ascorbic acid and dexamethasone for 2 dias to 21days. The microRNA or mRNA expression profiling during the differentiation process was analyzed through hybridizations with Agilent miRNA-microarray (8x15K format).
2014-11-28 | E-MTAB-3077 | biostudies-arrayexpress