DNMT3L is crucial for the osteogenesis ability of mesenchymal stem cells
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ABSTRACT:
PROVIDER: PRJNA454223 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7082710.fastq.gz | Fastqsanger.gz | |||
| SRR7082711.fastq.gz | Fastqsanger.gz | |||
| SRR7082712.fastq.gz | Fastqsanger.gz | |||
| SRR7082713.fastq.gz | Fastqsanger.gz | |||
| SRR7082706.fastq.gz | Fastqsanger.gz |
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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:Patterns of DNA methylation are established during gametogenesis. The catalytically-inactive adaptor Dnmt3L is crucial to ensure this occurs correctly. In vitro, Dnmt3L binds to the N terminal tail of histone H3 but the function of this interaction during development is unknown. Here we show that Dnmt3L-histone H3 interaction is necessary for spermatogenesis. Mutant animals exhibit reduced fertility, defective methylation establishment at retrotransposons coupled with their reactivation and meiotic catastrophe. The spermatogonial stem cell pool is also defective, with mutant cells displaying marked changes in gene expression. Genome-wide methylation analysis reveals reductions in CG methylation as well as severe loss of non-CG methylation suggesting that non-CG methylation is specifically sensitive to the ability of Dnmt3L to bind histone H3. MethylC-Seq of wild-type and Dnmt3LA/A 1dpp prospermatagonia
2015-01-14 | E-GEOD-58066 | biostudies-arrayexpress
Project description:Patterns of DNA methylation are established during gametogenesis. The catalytically-inactive adaptor Dnmt3L is crucial to ensure this occurs correctly. In vitro, Dnmt3L binds to the N terminal tail of histone H3 but the function of this interaction during development is unknown. Here we show that Dnmt3L-histone H3 interaction is necessary for spermatogenesis. Mutant animals exhibit reduced fertility, defective methylation establishment at retrotransposons coupled with their reactivation and meiotic catastrophe. The spermatogonial stem cell pool is also defective, with mutant cells displaying marked changes in gene expression. Genome-wide methylation analysis reveals reductions in CG methylation as well as severe loss of non-CG methylation suggesting that non-CG methylation is specifically sensitive to the ability of Dnmt3L to bind histone H3.
2015-01-14 | GSE58066 | GEO
Project description:Fetal mesenchymal stem cells promote osteogenesis via Notch signaling
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Project description:The core purpose of this project is to identify the novel epigenetic factors which play a crucial role on regulating stem cells developed from embryo development to ageing through the longitudinal analysis of their transcriptome, protein interactome, and post- translational modification network. Thus, this study would not only advance our understanding of epigenetic nature of stem cells through whole life, but also provide the novel strategy to develop the next generation stem cell therapeutics. According to our previous reports, we found that DNA methylation, particularly mediated by Dnmt3L could play a common epigenetic signature for modulating the stemness potency of both embryonic and adult stem cells. To investigate the post-translational modifications of Dnmt3L protein, we performed mass spectrometry analysis of Flag-tagged Dnmt3L proteins in murine embryonic stem cells (ESCs) and then identified several acetylated lysine residues. To examine their functional roles, we manufactured the lentivirus containing wild type Dnmt3L or the acetylated lysine mutants and they established the ESC cell lines stably harboring these constructs. To focus on epigenetic mechanism for stem cell biology, we will narrow down the key acetylated lysine sites of Dnmt3L, which can characteristically regulate the epigenetic status or transcription gene ontology. To get mechanistic insights, the transcriptome and DNA methylome features of the established ESC cell lines will be analyzed. The functional significance was examined by a series of experiments for in vitro and in vivo self-renewal and differentiation assays. Finally, we would extend these results to develop the efficient ex vivo expansion protocol for adult stem cells, particularly focusing on human mesenchymal stem cells. We expect that this proposal will not only advance our understating the epigenetic landscape of stem cell population but also contribute to establish the clinically best-suitable stem cell population. In addition, this study can be appliable to get a novel conceptional advances in other biological research such as cancer biology and ageing research.
2025-05-26 | PXD032953 | Pride
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:Crucial roles of mesenchymal Gata2 in murine epididymal development
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Project description:We used RRBS to analyze DNA methylation in mESC lines deficient for maternal Dnmt3L (Dnmt3L mKO), zygotic Dnmt3L (Dnmt3L KO), and both maternal and zygotic Dnmt3L (Dnmt3L mzKO). Compared to wild-type (WT) mESCs, Dnmt3L mKO mESCs exhibit severe loss of methylation at imprinted loci but no changes in global DNA methylation, Dnmt3L KO mESCs exhibit moderate loss of methylation at many Dnmt3a target regions but do not affect methylation at imprinted loci, and Dnmt3L mzKO mESCs exhibit combined changes of mKO and KO cells, with severe loss of methylation at imprinted loci and moderate loss of methylation at Dnmt3a target regions.
2018-10-04 | GSE116489 | GEO
Project description:Enhanced Osteogenesis of Mesenchymal Stem Cells Encapsulated in Injectable Microporous Hydrogel
| PRJNA1100418 | ENA