Ontology highlight
ABSTRACT:
PROVIDER: PRJNA999917 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Engineered Methylobacterium methanol batch exponential
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Project description:Engineered Methylobacterium methanol batch exponential strain CM702 vs. strain CM502
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Project description:Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by chondrocyte dysfunction and extracellular matrix degradation. While stem cell therapies have been constrained by immunological rejection risks, their derived extracellular vesicles (Exos) emerge as a promising alternative therapeutic approach. Antler, a remarkable regenerative organ with extraordinary regenerative capacity and chondrogenic potential, offers a unique biological resource. Antler Stem Cells (ASCs) provide an innovative extracellular vesicle source (ASC-Exos) that presents a compelling therapeutic strategy for addressing OA's complex pathogenesis. To investigate the therapeutic effects and mechanism of ASC-Exos in OA treatment. ASCs characteristics were confirmed through immunofluorescence and tri-lineage differentiation, while exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blot. A rat OA model was established to evaluate therapeutic effects of ASC-Exos via different administration routes. Small RNA sequencing identified key extracellular vesicle components, while dual-luciferase reporter assays confirmed regulatory interactions between miR-140 and metalloproteinase-13(MMP13). Stable miR-140 overexpressing ASCs were generated through lentiviral transduction. An IL-1β-stimulated chondrocyte OA model was employed to assess the impact of miR-140-engineered ASC-Exos (miR-140-Exos) on cellular proliferation, migration, and apoptosis. The therapeutic potential was further evaluated in in vivo animal models. We successfully isolated and characterized ASCs and ASC-Exos. Intra-articular injection of ASC-Exos demonstrated superior cartilage repair efficacy. The critical extracellular vesicle component miR-140 was identified. In vitro studies revealed that miR-140-Exos significantly enhanced chondrocyte proliferation and migration while reducing cellular apoptosis. Dual-luciferase assays confirmed miR-140 directly targets MMP13, with MMP13 overexpression partially reversing miR-140-mediated cellular effects. In vivo investigations demonstrated that miR-140-modified ASC-Exos effectively inhibited COL II degradation and suppressed NLRP3 elevation, thereby providing anti-inflammatory benefits and promoting cartilage regeneration. miR-140-Exos represent an innovative therapeutic approach for osteoarthritis, effectively promoting cartilage regeneration and alleviating inflammation through MMP13 inhibition, presenting a novel therapeutic strategy for OA treatment.
2025-09-03 | GSE306940 | GEO
Project description:MiR-140 is selectively expressed in cartilage. Deletion of the entire miR-140 locus in mice results in a growth retardation phenotype and an early-onset osteoarthritis-like pathology, however the relative contribution of miR-140-5p or miR-140-3p to the phenotype remains to be determined. An unbiased small RNA sequencing approach identified that miR-140-3p was in vast abundance (>10-fold) to miR-140-5p in human cartilage. Analysis of these data identified multiple miR-140-3p isomiRs differing from the miRBase [1] annotation at both the 5´ and 3´ end, with >99% of miR-140-3p isomiRs having one of two ‘seed’ sequences (5´ bases 2-8). The most abundant isomiR with each seed were selected for further analysis; miR-140-3p.2 which has an identical seed to the miRBase miR-140-3p (ACCACAG) and miR-140-3p.1 which has an altered seed (CCACAGG), and thus different potential targets. Each isomiR was overexpressed in chondrocytes and whole-genome transcriptomics used to identify targets. miR-140-3p.1 and miR-140-3p.2 significantly down-regulated 694 and 238 genes respectively (adj.P.Val<0.05), of which only 162 genes were commonly down-regulated by both isomiRs. Targets of both isomiRs were validated using 3´UTR luciferase assays. A significant enrichment of miR-140-3p.1 targets was identified within genes whose expression increase in the rib chondrocytes of Mir140-null mice and within genes whose expression decreased during human chondrogenesis. Finally, through imputing the expression of miR-140 from the expression of the host gene WWP2 in 124 previously published datasets an inverse correlation with miR-140-3p.1 predicted targets was identified. Together these data suggest the novel seed containing isomiR miR-140-3p.1 is more functional than the original consensus miR-140-3p or the isomiR with the same seed, miR-140-3p.2.
2020-07-17 | GSE144367 | GEO
Project description:MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders, but neomorphic (gain-of-new-function) mutations in miRNAs due to nucleotide substitutions have not been reported. Here we describe a neomorphic seed region mutation in the chondrocyte-specific, super-enhancer-associated MIR140 gene encoding microRNA-140 (miR-140) in a novel autosomal dominant human skeletal dysplasia. Mice with the corresponding single nucleotide substitution show skeletal abnormalities similar to those of the patients but distinct from those of miR-140-null mice. This mutant miRNA gene yields abundant mutant miR-140-5p expression without miRNA-processing defects. In chondrocytes, the mutation causes widespread derepression of wild-type miR-140-5p targets and repression of mutant miR-140-5p targets, indicating that the mutation produces both loss-of-function and gain-of-function effects. Furthermore, the mutant miR-140-5p seed competes with the conserved RNA-binding protein Ybx1 for overlapping binding sites. This finding may explain the potent target repression and robust in vivo effect by this mutant miRNA even in the absence of evolutionary selection of miRNA–target RNA interactions, which contributes to the strong regulatory effects of conserved miRNAs. Our study presents the first case of a pathogenic gain-of-function miRNA mutation and provides molecular insight into neomorphic actions of emerging and/or mutant miRNAs.
2019-01-29 | GSE98306 | GEO
Project description:Proteogenomic analysis of Methylobacterium extorquens DM4 using the dN-TOP strategy with heavy and light TMPP labelling
2018-04-25 | PXD006836 | Pride
Project description:Differential analysis of Methylobacterium extorquens DM4 in methanol versus dichloromethane condition using shotgun label free MS1 quantification approach
2018-04-25 | PXD006838 | Pride