Transcriptomic analysis of ETV2-overexpressing human dental pulp stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE160451 | GEO | 2022/10/12
REPOSITORIES: GEO
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Project description:DPSCs derivedgenerated from the three different donors were transfectedinfected with ETV2-overexpressing lentiviralrus particles or control lentiviralus particles. Protein samples were harvested after 10 days of endothelial differentiation. Proteome profiling was performed by the iProteome platform of the Fudan University Human Phenome Institute according to user guide.
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2015-09-30 | GSE73548 | GEO
Project description:Lineage commitment and tumorigenesis specify adult stem cells from different tissues or organs. To gain insight into the mechanism of this programming, phenotypic, functional and transcriptome analyses were performed in mesenchymal stem cells derived from human dental pulp (DPSCs) and bone marrow (BMSCs). DPSCs and BMSCs had similar morphologies and flow cytometric profiles, and were capable of tri-lineage differentiation into osteoblast, adipocyte and chondocyte. However, compared with BMSCs, DPSCs increased in osteogenic potential, decreased in adipogenic potential, and formed dentin-pulp-like complexes in vivo. Genome-wide RNA-seq and differential expression analysis revealed that signalings such as, phosphatase and tensin homolog (PTEN)/PI3K/AKT pathway, and cancer-related pathway were different in both cells. Differential PTEN expression, higher in DPSCs than BMSCs, was responsible for the lineage commitment and tumorigenesis differences in both cells. Besides, BMSCs decreased in PTEN DNA methylation compared to DPSCs, which was mediated by increased DNA (cytosine-5) methyltransferase 3B (DNMT3B) expression. Furthermore, histone methyltransferase G9a mediated repressive epigenetic mark H3K9Me2 was selectively enriched in BMSCs. Moreover, DPSCs were more resistant to oncogenic transformation than BMSCs. To link lineage commitment with tumorigenesis, we demonstrated that DPSCs were more resistant to oncogenic transformation than BMSCs and PTEN deficiency increased the sensitivity of DPSCs for tumorigenic transformation. The results help understanding the roles of the epigenetic factors in lineage commitment and tumorigenesis and also for therapeutic uses of adult stem cells.
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Project description:To evaluate the miRNA and mRNA expression profiles (miRNOME and transcriptome) we reconstructed networks identifying miRNAs and mRNA 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 to 21 days. The microRNA or mRNA expression profiling during the differentiation process was analyzed through hybridizations with Agilent miRNA-microarray (8x15K format) or whole-human genome Agilent microarray (4x44K format).
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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.
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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.
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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.
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