Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648
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ABSTRACT:
PROVIDER: PRJNA513041 | ENA |
REPOSITORIES: ENA
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Project description:Histone arginine methylation, which is catalyzed by protein arginine methyltransferases (PRMTs), plays a key regulatory role in various biological processes, including signal transduction, RNA splicing, transcription and chromatin remodeling, and DNA repair. Several PRMTs are involved in skeletal development; however, their role in the osteogenic differentiation of mesenchymal stem cells (MSCs) is not completely clear. In this study, we aimed to elucidate the function of PRMT3, a type-I PRMT that catalyzes the formation of ω-mono- or asymmetric dimethyl arginine, in MSC osteogenesis. We found that PRMT3 is involved in MSC osteogenic commitment and bone remodeling. Then we did PRMT3 and H4R3me2a ChIP-seq in MSC to find the possible target genes.
2019-08-20 | GSE124674 | GEO
Project description:Fetal mesenchymal stem cells promote osteogenesis via Notch signaling
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Project description:Histone arginine methylation, which is catalyzed by protein arginine methyltransferases (PRMTs), plays a key regulatory role in various biological processes. Several PRMTs are involved in skeletal development; however, their role in the osteogenic differentiation of mesenchymal stem cells (MSCs) is not completely clear. In this study, we aimed to elucidate the function of PRMT3, a type-I PRMT that catalyzes the formation of ω-mono- or asymmetric dimethyl arginine, in MSCs osteogenesis. We found that PRMT3 promoted MSCs osteogenic commitment and bone remodeling. PRMT3 activated the expression of miR-3648 by enhancing histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) levels at promoter region of the gene. Overexpression of miR-3648 rescued impaired osteogenesis in PRMT3-deficient cells. Moreover, administration of Prmt3 shRNA or a chemical inhibitor of PRMT3 (SGC707) caused an osteopenia phenotype in mice. These results indicate that PRMT3 is a potential therapeutic target for the treatment of bone regeneration and osteopenia disorders.
| S-EPMC6680051 | biostudies-literature
Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
2013-09-01 | E-MTAB-1828 | biostudies-arrayexpress
Project description:Bone development and repair depends on the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. MSCs can be differentiated towards osteoblasts in vitro, making these cells a convenient tool for investigation of osteogenesis. Molecular characterization of this process is relevant for the application of MSCs in skeletal regenerative medicine, and for understanding the deregulation of osteogenesis in bone disease. Cellular differentiation is driven by highly regulated changes in gene expression, which at the level of transcription is associated with DNA binding of transcriptional regulators and local changes in chromatin landscape. By sequencing of RNA (RNA-Seq) and immunoprecipitated chromatin (ChIP-Seq) we have characterized gene expression, histone modification changes and DNA binding of the bone master regulator RUNX2 in osteogenic differentiation. Data from the RNA-Seq experiment has also been deposited at ArrayExpress under accession number E-MTAB-1829 (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1829/).
2013-09-01 | E-MTAB-1829 | biostudies-arrayexpress
Project description:DNA methyltransferase 3-like (DNMT3L), an epigenetic modulating factor known to participate in facilitating de novo DNA methylation with DNMT3A and DNMT3B, is mainly expressed in pluripotent stem cells and germ cells. We observed that Dnmt3l deficiency imped mesenchymal stem cells (MSCs) self-renewal and proliferation by colony forming unit – fibroblast (CFU-F) assay and growth curve test. Furthermore, calcium precipitation is dramatically decreased after 14 days of osteogenic induction in Dnmt3l KO mice derived MSCs. We further investigated the gene expression pattern in undifferentiated and day 3 of osteogenic induction MSCs derived from wild type and Dnmt3l KO mice respectively by RNA-sequencing, and found that differentially expressed genes (DEGs) before osteogenesis are highlighted in various pathways related to bone and the DEGs from day 3 of osteogenic induction MSCs are associated with proliferation and differentiation. Collectively, these results indicate that Dnmt3l deficiency abrogated MSCs property and may play role in MSC differentiation potential. By these results, we suggested that transiently expressed DNMT3L in pluripotent stem cells contribute to mediation of epigenetic mark establishment and have a lasting effect in mesenchymal stem cells.
2021-03-16 | GSE113844 | GEO
Project description:miR-375 play an important role in regulating the osteogenesis in human adipose tissue-derived mesenchymal stem cells, following specific genes are up-regulated or down-regulated. We used microarrays to detail the global programme of gene expression underlying osteogenesis and identified distinct classes of up-regulated genes or down-regulated genes during this process.
2016-09-22 | GSE87160 | GEO
Project description:Enhanced Osteogenesis of Mesenchymal Stem Cells Encapsulated in Injectable Microporous Hydrogel
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Project description:DNMT3L is crucial for the osteogenesis ability of mesenchymal stem cells
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Project description:Objectives: Bone marrow mesenchymal stem cells (BMSC) play an important role in osteogenesis. However, the role of BMSC in osteopenia in spinal tuberculosis (STB) patients is unclear. Methods: Bone mineral density (BMD) of 53 STB patients and 55 controls was measured. The migration and osteogenesis of BMSC were assessed by wound healing assays and alizarin red staining, and osteoclast marker expression was measured. RNA-seq was performed on BMSC and the enriched signaling pathways were verified. Results:BMD of STB patients was significantly decreased and BMSC migration and osteogenesis were significantly reduced. After verification, we found that the B-cell receptor signaling pathway, tuberculosis, osteoclast differentiation, Th17-cell differentiation, Ras signaling pathway and PI3K-Akt signaling pathway were affected.And of these pathways, the B-cell receptor signaling, Th17-cell differentiation, Ras signaling pathway and PI3K-Akt signaling pathway were not previously known to be involved in osteopenia. The MAPK signaling pathway and ECM-receptor interactions were correlated with STB prognosis. Conclusion: STB infection can significantly reduce BMSC migration and osteogenesis, decreasing BMD. This process is regulated by multiple pathways and is associated with STB prognosis. Our study suggests that reduced BMSC migration and osteogenesis play important roles in osteopenia in STB patients, and BMSC may be a therapeutic target.
2023-12-01 | GSE222013 | GEO