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Metabolism as an early predictor of DPSCs aging

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE123973 | GEO | 2018/12/18

REPOSITORIES: GEO

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Metabolism as an early predictor of DPSCs aging

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

DNA methylation analysis of three distinct human odontogenic stem cells

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

Proteomic profile of human stem cells from dental pulp and periodontal ligament

Project description:Dental stem cells isolated from oral tissues have been shown to provide with high proliferation ability and multi-lineage differentiation potential. Although the dental stem cells possess the potential of nerve regeneration, the specific expression profile of dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are still unclear. Here, DPSCs and PDLSCs, collected from the same tooth with 3 donors, were tested for high-throughput protein profiles by combining two-dimensional gel proteomics and TMT-based proteomics.

2021-06-10 | PXD021997 | Pride

Development of gene expression signatures for SOX2 overexpressing human dental pulp stem cells

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

Genome-wide maps of mRNAs and ncRNAs in aging and young dental pulp stem cells

Project description:Purpose: The goals of this study are to compare differentially expressed genes in young dental pulp stem cells to the aging dental pulp stem cells and to predict key regular factors. Methods: mRNA and ncRNA profiles of young and aging dental pulp stem cells were generated by deep sequencing, using BGISEQ-500 platform (BGI-Shenzhen, China). The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Agilent Technologies 2100 system and real-time quantitative PCR (QPCR) (TaqMan Probe). Results:After filtering out adaptor-related and low-quality sequences, 669 million clean reads in mRNA Library were generated. Clean reads was mapped to genome sequence with the mapping ratio from 88.54% to 97.61%. A total of 230487 mRNAs was obtained including 123724 known mRNAs and 106763 novel mRNAs respectively; In addition, we detected 177880 lncRNAs，139743 and 38137 were known and novel. For correlation analysis, the coefficient we obtained were all greater than 0.90, indicating a high biological correlation Conclusions: Our study represents the first detailed analysis of differentially expressed genes in aging and young dental pulp stem cells, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that hsa-miR-6724-5p may be a key node in the aging process of DPSCs, and its target genes was involved in the dopaminergic synapse

2021-11-28 | GSE185751 | GEO

LC-MS and gel-based comparison of DPSCs and PDLSCs

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

Identification of mirna during osteoblast differentiation of human dental pulp stem cells

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

Rejuvenation of Human Stem Cells from Aged Dental Pulp by High Concentration of Serum Culture ex vivo

Project description:Adult stem cells maintain tissue integrity by continuous cellular turnover or serving progenitor cells. Human dental pulp stem cells (hDPSCs) are adult stem cells that can readily be isolated from extracted teeth, then expanded or stored for tissue repair and regeneration. However, stem cells undergo an aging process characterized by a decline in functional abilities, leading eventually to reduced organ function and delays in tissue repair. Like other stem cells, hDPSCs age and go through cellular senescence but little information is available on the mechanisms of aging or the details of the aged hDPSC phenotype. In this study, we investigated the aging phenotypes of human dental pulp and hDPSCs and attempted to rejuvenate them. In this study, hDPSCs were isolated from 23 third molars and primary cultured. Then, Flow cytometey, growth curve, dubling time, colony-forming-unit assay, cell viability after cryopreservation and in serum-free media culture, differntiation capacity for odonto-, adipo- and chondrogenesis, and RNA sequencing were analyzed. As results, the aged tooth maintained its weight of dental pulp however, the frequency of CD90+CD73+ mesenchymal stem cells inside pulp significantly decreased with donor aging. Moreover, each aged hDPSCs showed lower proliferative abilities, poorer survival rates, decreased tri-differentiation potential, and decline in metabolic activities than young hDPSCs. We also found those aged phenotypes could be recovered by cultivating aged hDPSCs in high concentration of fetal bovine serum (FBS) ex vivo and furthermore, the declined metabolic activities were restored by the culture. Here, we suggest a novel method of intervention for rejuvenating hDPSCs and these results have applications in both regenerative medicine and stem cell biology.

2021-01-28 | GSE165627 | GEO

Single cell transcriptional profiling of mouse molar and incisor tooth assembloids

Project description:Throughout the various stages of tooth development, reciprocal epithelial-mesenchymal interactions are the driving force, for instance crucially involved in the differentiation of mature enamel-forming ameloblasts and dentin-producing odontoblasts. Here we established mouse tooth ‘assembloids’, comprised of tooth organoid-derived dental epithelial cells (from mouse molars and incisors) cultured together with molar dental pulp stem cells (DPSCs), to mimic these developmental interactions. Assembloids from both tooth types were grown both in basal- and differentiation-inducing conditions. Single cell transcriptomics analysis was applied to in detail characterize and validate the newly developed mouse tooth assembloid model and evaluate the induced differentiation processes.

2023-04-19 | E-MTAB-12544 | biostudies-arrayexpress

Integrative epigenomic and transcriptomic anlaysis of odontogenic differentiation of dental pulp stem cells [ATAC-seq]

Project description:Chromatin accessibility is key epigenomic regulatory mechanisms of transcription. Herein, to profile open chromatin maps and transcriptional feature associated with odontogenic tropism of dental pulp stem cells (DPSCs), we conducted integrative analysis of epigenomic alteration and transcriptome changes during odontogenic differentiation of DPSCs. DPSCs were long-term cultured in odontogenic induction medium to evaluate differentiation abilities. ATAC-seq and RNA-seq samples were collected before and after the 9-day culture. One of the day 9 specific-super-enhancer was constructed in ALPL (Alkaline Phosphatase, Biomineralization Associated) intragenic region in which all the day 9-specific open chromatin peaks were included and BMP-mediated Smad binding element are specifically accumulated. These results suggest that the specific local chromatin regions were selectively opened and, particularly, super-enhancers were constructed, which was able to guide differentiative transcriptional factors such as Smad1/4 to their target gene loci in differentiating DPSCs; hence, epigenetic modifications such as histone deacetylase (HDACs) inhibitor application have therapeutic potential for DPSCs-induced dentin/pulp regeneration.

2023-09-29 | GSE244058 | GEO

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