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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244057 | GEO | 2023/09/29

REPOSITORIES: GEO

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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

Characterization of odontogenic differentiation from human dental pulp stem cells using TMT-based proteomic analysis

Project description:The repair of dental pulp injury relies on the odontogenic differentiation of dental pulp stem cells (DPSCs). To better understand the odontogenic differentiation of DPSCs and identify proteins involved in this process, tandem mass tags (TMTs) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were applied to compare the proteome profiles of induced and control DPSCs. The proteins expressed during osteogenic differentiation of human DPSCs were profiled using the TMT method combined with LC-MS/MS analysis. The identified proteins were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then a protein-protein interaction (PPI) network was constructed. Two selected proteins were confirmed by western blot (WB) analysis. A total of 223 proteins that were differentially expressed were identified. Among them, 152 proteins were significantly upregulated and 71 were downregulated in the odontogenic differentiation group compared with the control group. On the basis of biological processes in GO, the identified proteins were mainly involved in cellular processes, metabolic processes, and biological regulation, which connected with the signaling pathways highlighted by KEGG pathway analysis. PPI networks showed that most of the differentially expressed proteins were implicated in physical or functional interaction. The protein expression levels of FBN1 and TGF-β2 validated by WB were consistent with the TMT analysis. This is the first proteomic analysis of human DPSC odontogenesis using a TMT method. We identified many new differentially expressed proteins that are potential targets for pulp-dentin complex regeneration and repair.

2021-09-09 | PXD021279 | 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

Differential expression of long noncoding RNAs of dental pulp stem cells in the SDF-1α induced

Project description:We triggered the involvement of lncRNAs in odontogenic differentiation of DPSCs by incubation with SDF-1α. By LncRNA microarray, alterations in lncRNA expression at odontogenic differentiation inducted by 100ng/Ml SDF-1α were identified. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate several random upregulated and downregulated LncRNAs in the odontogenic differentiation of DPSCs. In addition, Gene ontology (GO) analysis and coding-noncoding gene coexpression (CNC) analysis were conducted to predict the interactions of coding and noncoding RNA and identify core regulatory factors in odontogenic differentiation of DPSCs.

2021-09-02 | GSE183162 | GEO

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

Extracellular matrix derived from dental pulp stem cells promotes osteogenic differentiation of gingival fibroblasts via Wnt and Hippo signaling pathway

Project description:This study investigated the efficacy of decellularized ECM derived from human dental pulp stem cells (dECM_DPSCs) and gingival-derived mesenchymal stem cells (dECM_GSCs) as an inductive scaffold for osteogenic differentiation of GSCs. ECM was constructed from DPSCs and GSCs that were cultured in a growth medium supplemented with L-ascorbic acid (N-ECM) or osteogenic induction medium (OM-ECM). The gene expression profile was examined using a high-throughput RNA sequencing technique.

2024-03-27 | GSE226347 | GEO

Effects of endogenous GDF11 on the odontogenic differentiation of dental pulp stem cells

Project description:Knockdown of endogenous GDF11 downregulated the odontogenic differentiation of human dental pulp stem cells (hDPSCs). We performed RNA-seq analysis on hDPSCs transfected with GDF11 small interfering RNA (siRNA) and control siRNA after 7 days of odontogenic induction, in order to investigate the underlying mechanisms of endogenous GDF11 regulating odontogenic differentiation in hDPSC.

2020-06-03 | GSE151435 | GEO

Enhancer Mapping in Chronic Lymphocytic Leukemia

Project description:<p>In this study we profile the epigenomic enhancer landscapes of CLL B cells (CD19+/CD5+) harvested from peripheral blood of patients from our Center. Included are results of ChIPseq profiling using chromatin immunoprecipitation of the enhancer histone mark H3K27ac (acetylated lysine 27 on histone H3), and open chromatin profiles using ATAC-seq (assay for transposase accessible chromatin). These profiles are used to define the global enhancer and super enhancer landscape of CLL B cells, and to derive active transcription factor networks associated with this disease. Also included are H3K27ac ChIP-seq and ATAC-seq datasets for non-CLL B cells obtained from the peripheral blood of normal adult donors.</p>

| phs001704 | dbGaP

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

Temporal enhancer profiling of parallel lineages identifies AHR and GLIS1 as regulators of mesenchymal multipotency

Project description:Temporal data on gene expression and context-specific open chromatin states can improve identification of key transcription factors (TFs) and the gene regulatory networks (GRNs) controlling cellular differentiation. However, their integration remains challenging. Here, we delineate a general approach for data-driven and unbiased identification of key TFs and dynamic GRNs, called EPIC-DREM. We generated time-series transcriptomic and epigenomic profiles during differentiation of mouse multipotent bone marrow stromal cells (MSCs) towards adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages and identifed the shared TFs involved in both differentiation processes. To take an alternative approach to prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic MSC-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and we propose they function as guardians of mesenchymal multipotency.

2019-02-07 | E-MTAB-6840 | biostudies-arrayexpress

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