Stage-specific requirement for Mettl3-dependent m6A mRNA methylation during hematopoietic stem cell differentiation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA509123 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8309100_1.fastq.gz | Fastqsanger.gz | |||
| SRR8309100_2.fastq.gz | Fastqsanger.gz | |||
| SRR8309110_1.fastq.gz | Fastqsanger.gz | |||
| SRR8309110_2.fastq.gz | Fastqsanger.gz | |||
| SRR8309120_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 104 |
Similar Datasets
Project description:Hematopoietic stem cells (HSCs) maintain balanced self-renewal and differentiation according to physiological demands, but how different facets of these functions are precisely regulated is not fully understood. N6-methyladenosine (m6A) mRNA methylation has emerged as an important mode of epitranscriptional gene expression regulation affecting many biological processes. We show that deleting the m6A methyltransferase, Mettl3, from the adult hematopoietic system led to an accumulation of HSCs in the bone marrow and marked reduction of HSC reconstitution potential due to a blockage of HSC differentiation. Interestingly, deleting Mettl3 from myeloid cells using Lysm-cre did not have any discernable impact on myeloid cell number or function. m6A sequencing on purified HSCs revealed 2,073 genes with significant m6A modification. In particular, Myc, a key regulator of HSC differentiation, was identified as a direct target of m6A in HSCs. Mettl3-deficient HSCs failed to up-regulate Myc expression upon stimulation to differentiate and enforced expression of Myc rescued differentiation defects of Mettl3-deficient HSCs. Our results thus revealed a key role of m6A in governing HSC differentiation by regulating Myc expression. This data includes m6A sequencing data on HSCs from wild-type or Mettl3-deficient mice, revealing the Mettl3-depedent m6A targets in HSCs.
2019-03-31 | GSE123525 | GEO
Project description:Background: N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological events and is implicated in various metabolic-related diseases. However, its role in MASLD remains unclear. This study aims to investigate the impact of Mettl3 on MASLD through multi-omics analysis, with a focus on exploring its potential mechanisms of action. Methods: MASLD mouse models were established by feeding a high-fat diet for 12 weeks, and Mettl3 stable overexpression AML12 cell models were constructed via lentiviral transfection. Subsequent transcriptomic and proteomic analyses, as well as integrated analysis between different omics datasets, were conducted. Results: Mettl3 expression significantly increased in MASLD mouse models. In the transcriptomic and proteomic analyses, we identified 848 genes with significant inconsistencies between transcriptomic and proteomic datasets. GO/KEGG enrichment terms may involve post-transcriptional modifications, particularly Mettl3-mediated m6A modification. Subsequently, through integrated proteomic analysis of Mettl3-overexpressed AML12 cell models and MASLD mouse models, we selected the top 20 co-upregulated and co-downregulated GO/KEGG terms as the main biological processes influenced by Mettl3 in MASLD. By intersecting with pathways obtained from previous integrated analyses, we identified GO/KEGG terms affected by Mettl3-induced m6A modification. Protein-protein interaction analysis of proteins involved in these pathways highlighted GAPDH, ENO1, and TPI1 as three key hub genes. Conclusion: In MASLD, Mettl3 regulates the glycolytic pathway through m6A modification, influencing the occurrence and development of the disease via the key hub genes GAPDH, ENO1, and TPI1. These findings expand our understanding of MASLD and provide strong evidence for potential therapeutic targets and drug development.
2024-09-20 | PXD050565 | Pride
Project description:The N6-methyladenosine (m6A) mRNA modification and the mitochondrial respiratory chain (MRC) hold paramount importance in the advancement of MASLD. This study thoroughly investigates the relationship and impact of m6A mRNA modification and mitochondrial function in the progression of MASLD. Here we report that the mRNA and protein levels of mitochondrial respiratory chain (MRC) subunits showed inconsistent trends in vivo experiments. Abnormal m6A modification and mitochondrial dysfunction in MASLD were attributed to the upregulation of methyltransferase like 3 (Mettl3) and the downregulation of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) induced by high-fat foods. Mettl3 promoted the MRC's function. However, knockout of the reader protein YTHDF1, which plays a crucial role in the m6A modification process, counteracted the effect of Mettl3 and suppressed MRC. In MASLD, damage to the MRC may be regulated by the Mettl3-m6A-YTHDF1 complex axis, especially by the role of YTHDF1. Our research has offered a novel perspective on the involvement of m6A mRNA methylation in the pathogenesis of MASLD.
2024-09-20 | PXD047819 | Pride
Project description:Mettl3 regulates late-stage retinogenesis and mouse retina m6A epitranscriptome
| PRJNA749616 | ENA
Project description:Genomic and transcriptomic alterations are insufficient to explain the variance in protein expression seen in cancer. Recent evidence has highlighted the role of N6-methyladenosine (m6A) in the regulation of mRNA expression, stability and translation, supporting a potential role for post-transcriptional regulation mediated by m6A in cancer. Here we explore prostate cancer as an exemplar cancer and generate the first prostate m6A maps, and further examined how low levels of N6-adenosine-methyltransferase (METTL3) associates with advanced prostate cancer and results in altered expression at the level of transcription, translation, and protein. In particular extracellular matrix proteins have a high number of m6A sites and show significant changes in expression with METTL3 knock-down. We also discovered the upregulation of a hepatocyte nuclear factor-driven gene signature that is associated with therapy resistance in prostate cancer. Significantly, METTL3 knock-down rendered the cells resistant to androgen receptor antagonists, implicating changes in m6A as a mechanism for therapy resistance in metastatic prostate cancer.
2021-06-07 | PXD022348 | Pride
Project description:Hematopoietic stem cells (HSCs) maintain balanced self-renewal and differentiation according to physiological demands, but how different facets of these functions are precisely regulated is not fully understood. N6-methyladenosine (m6A) mRNA methylation has emerged as an important mode of epitranscriptional gene expression regulation affecting many biological processes. We show that deleting the m6A methyltransferase, Mettl3, from the adult hematopoietic system led to an accumulation of HSCs in the bone marrow and marked reduction of HSC reconstitution potential due to a blockage of HSC differentiation. Interestingly, deleting Mettl3 from myeloid cells using Lysm-cre did not have any discernable impact on myeloid cell number or function. m6A sequencing on purified HSCs revealed 2,073 genes with significant m6A modification. In particular, Myc, a key regulator of HSC differentiation, was identified as a direct target of m6A in HSCs. Mettl3-deficient HSCs failed to up-regulate Myc expression upon stimulation to differentiate and enforced expression of Myc rescued differentiation defects of Mettl3-deficient HSCs. Our results thus revealed a key role of m6A in governing HSC differentiation by regulating Myc expression. This data includes RNA-Seq analysis to showing only minor gene expression changes in adult bone marrow murine hematopoietic stem cells 10 days after Mettl3 deletion by pIpC administration compared to pIpC treated controls.
2019-03-31 | GSE123526 | GEO
Project description:Mettl3-dependent m6A targets in adult murine hematopoietic stem cells
| PRJNA509125 | ENA
Project description:N6-methyladenosine (m6A) is the most abundant RNA modification, but little is known about its role in mammalian hematopoietic development. Conditional deletion of the m6A writer METTL3 in murine fetal liver results in hematopoietic failure and perinatal lethality. Loss of METTL3 and m6A activates an aberrant innate immune response, mediated by the formation of endogenous double-stranded RNAs (dsRNAs). The aberrantly formed dsRNAs are long, highly m6A modified in their native state, characterized by low folding energies and predominantly protein-coding. We identified coinciding activation of innate immune pattern recognition receptor pathways normally tasked with the detection of foreign dsRNAs. Our results suggest that m6A modification protects against endogenous dsRNA formation and a deleterious innate immune response during mammalian hematopoietic development. Keywords: innate immune response, dsRNA, RNA modification, N6-methyladenosine, METTL3, hematopoietic development, RNA-seq, H3K4me3, CUT&RUN, J2-RIP, dropseq, single cell RNA-seq, scRNA-seq, LSK, fetal liver
2020-06-01 | GSE148882 | GEO
Project description:The goal of this study is to determine the critical requirement of N6-Methyladenosine (m6A) methyltransferase Mettl3 during CD8+ T cell responses upon acute viral infection. We demonstrate that conditional ablation of Mettl3 in CD8+ T cells impairs effector expansion and terminal differentiation in an m6A-dependent manner, which in turn affects memory formation and secondary response. Mechanism analysis indicates that Mettl3 deficiency broadly affects expression of cell cycle and transcriptional regulators. Based on these findings, our study reveals the important role of m6A modification in CD8+ T cell responses.
2024-06-01 | GSE215760 | GEO
Project description:METTL3-mediated RNA N6-methyladenosine (m6A) is the most prevalent modification participates in tumor initiation and progression via regulating expression of their target genes in cancers. However, its role in tumor cell metabolism remains poorly appreciated. In this study, we conducted a multi-omics analysis including m6A microarray and quantitative proteomics to explore the potential effect and mechanism of METTL3 on the metabolism in gastric cancer cells. Our results found that significant alterations in the protein and m6A modification profile which induced by METTL3 overexpression in GC cells. Gene Ontology (GO) enrichment results showed that down-regulated proteins were significantly enriched in intracellular mitochondrial oxidative phosphorylation (OXPHOS), and the Protein-Protein Interaction (PPI) network analysis found that these differentially expressed proteins were significantly associated with OXPHOS. Subsequently, a prognostic model constructed based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the high-risk group showed a worse prognosis in GC patients. Meanwhile, the Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in the energy metabolism signaling pathway. Then, combined with the results of the m6A microarray analysis, the intersection molecules of DEPs and differential methylation genes (DMGs) were significantly correlated with the genes involved in OXPHOS. Besides, there were also significant differences in prognosis and GSEA enrichment between the two clusters of GC patients classified according to consensus clustering algorithm. Finally, we focused on highly expressed, highly methylated molecules regulated by METTL3 and identified three (AVEN, DAZAP2, DNAJB1) genes that were significantly associated with poor prognosis in patients with GC. These results indicated that METTL3-regulated DEPs in GC cells were significantly associated with OXPHOS. After combined with m6A microarray analysis, the results suggested that these proteins might be involved in cell energy metabolism through m6A modifications thus influencing the prognosis of GC patients. Overall, our study revealed that METTL3 involved in cell metabolism through an m6A-dependent mechanism in GC cells, and indicated a potential biomarker for prognostic prediction in GC.
2023-03-10 | PXD036773 | Pride