Identification of 5-methylcytosine associated genes in osteoarthritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE235610 | GEO | 2023/09/20
REPOSITORIES: GEO
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Project description:Our study aimed to identify common m6A features in OA. We identified 8511 genes with 25295 peaks in the OA sample and 7541 genes with 17474 peaks in the control sample, indicating an overall hypermethylated level in the OA cartilage.
2023-12-25 | GSE221415 | GEO
Project description:5-methylcytosine (m5C) is a type of RNA modifications reported to regulate diverse biological processes. However, the distribution and biological functions of m5C in E. tenella mRNAs remain largely unknown. Herein, we report transcriptome-wide profiling of mRNA m5C in E. tenella by applying m5C RNA immunoprecipitation followed by a deep-sequencing approach (m5C-RIP-seq). Our data showed that m5C peaks were distributed across the whole mRNA body. There were 2813 hypermethylated and 1850 hypomethylated m5C peaks in sporulated oocysts compared with unsporulated oocysts. Further joint analysis showed a positive correlation between m5C modification and gene expression levels. The mRNA sequencing and m5C-RIP-seq data were consistent with the results of the quantitative reverse transcription PCR (RT-qPCR) and m5C-RIP-qPCR, respectively. Gene ontology (GO) and pathway enrichment analysis predicated diverse biological functions and pathways, including microtubule motor activity, helicase activity, cGMP-PKG signaling pathway, aminoacyl-tRNA biosynthesis, glycolysis/gluconeogenesis and spliceosome. Meanwhile, stage-specific gene expression signatures of m5C-related enzymes were observed. Altogether, our findings revealed the transcriptional significance of m5C modification in E. tenella oocysts, providing clues for in-depth research.
2023-12-19 | GSE249232 | GEO
Project description:Methylation of carbon 5 in cytosine (5-methylcytosine; m5C) is a well-characterized DNA modification, and is also predominantly reported in highly abundant noncoding RNAs, such as rRNA and tRNA, in both prokaryotes and eukaryotes. However, the distribution and biological functions of m5C in plant mRNAs remain largely unknown. Here we develop an m5C RNA immunoprecipitation followed by deep sequencing approach (m5C-RIP-seq) to achieve transcriptome-wide profiling of RNA m5C in Arabidopsis thaliana. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and dot blot analyses reveal a dynamic pattern of m5C mRNA modification in various tissues and at different developmental stages. m5C-RIP-seq analysis identifies 6,045 putative m5C peaks in 4,465 expressed genes in young seedlings. m5C is enriched in coding sequences with two peaks located immediately after start codons and before stop codons, and is associated with mRNAs with low translation activity. We further show that a RNA (cytosine-5)-methyltransferase, tRNA specific methyltransferase 4B (TRM4B), exhibits the m5C mRNA methyltransferase activity. Mutations in TRM4B display defects in root development and decreased m5C levels in root mRNA. Furthermore, TRM4B affects transcript levels of the genes involved in root development, which is positively correlated with their mRNA stability and m5C levels. Our results suggest that m5C in mRNA is a new epitranscriptome marker widely distributed in plant genes, and that regulation of this modification is an integral part of gene regulatory networks underlying plant development.
2017-10-05 | GSE94022 | GEO
Project description:Objectives: To identify novel gene transcripts and biological processes in meniscus from patients with and without osteoarthritis (OA). Methods: We used microarrays to identify gene transcripts differentially expressed in meniscus tissues obtained from OA and non-OA patients (N=12 each). Real-time PCR was performed on selected gene transcripts. Biological processes and gene networking was examined computationally. Transcriptome signatures from OA and non-OA meniscus were mapped with 37 previously published gene transcripts differentially expressed between healthy and OA cartilage to evaluate how meniscus gene expression relates to cartilage with this disease. Results: We identified 168 gene transcripts that were significantly differentially expressed between OA (75 elevated, 93 repressed) and non-OA samples (≥1.5-fold). Among these, CSN1S1, COL10A1, WIF1, SPARCL1 and DEFA3 were the most prominent gene transcript elevated in OA meniscus and POSTN, VEGFA, CEMIP, COL6A3 and SOX11 were repressed in OA meniscus. Gene transcripts elevated in OA meniscus represented response to external stimuli, cell migration and localization while those repressed in OA meniscus represented histone deacetylase activity and skeletal development. Numerous long lncRNAs were differentially expressed between the two samples. When segregated by OA-associated gene transcripts, we observed three distinct clustering patterns of OA and non-OA meniscus. Conclusions: These data provide novel evidence for a role of epigenetically regulated histone deacetylation in meniscus tears as well as expression of lncRNAs. Patient clustering based on OA-associated gene transcripts confirmed that the meniscus in OA knees exhibited OA phenotype while injured meniscus demonstrated some signs towards OA.
2017-12-27 | GSE98918 | GEO
Project description:In an effort to identify novel differentially-expressed genes in OA, we performed RNA-seq analysis using cartilage isolated from nonarthritic and OA patients. Total RNA was isolated from 3 samples of nonarthritic cartilage and 4 samples of OA cartilage (Kellgren-Lawrence Grade 3 or 4). Genes (900 total, 600 up-regulated, 300 down-regulated) were differentially expressed in OA vs. normal (fold change > 2, FDR < 0.00001, adjusted p < 0.05). Gene set enrichment analysis (GSEA) indicated altered gene expression pattern in OA cartilage compared with nonarthritic cartilage. Specifically, pathways known to be implicated in OA pathogenesis, including inflammatory response, interferon alpha and gamma response, apoptosis, and oxidative phosphorylation, were up-regulated in OA cartilage compared with nonarthritic cartilage.
2022-03-10 | GSE168505 | GEO
Project description:Osteoarthritis (OA) is a polygenic disease of older people resulting in the breakdown of cartilage within articular joints. Although a leading cause of disability, there are no disease-modifying therapies. Evidence is emerging to support the origins of OA in skeletogenesis. Whilst methylation QTLs (mQTLs) co-localizing with OA GWAS signals have been identified in aged human cartilage and used to identify effector genes and variants, such analyses have never been conducted during human development. Here, for the first time, we have investigated the developmental origins of OA genetic risk at seven well-characterized OA risk loci, comprising 39 OA-mQTL CpGs, in human fetal limb (FL) and cartilage (FC) tissues using a range of molecular genetic techniques. We compared our results to aged cartilage samples (AC) and identified significant OA-mQTLs at 14 CpGs and 29 CpGs in FL and FC tissues, respectively. Differential methylation was observed at 26 sites between fetal and aged cartilage, with the majority becoming actively hypermethylated in old age. Notably, 6/9 OA effector genes showed allelic expression imbalances during fetal development. Finally, we conducted ATAC-sequencing in cartilage from the developing and aged hip and knee to identify accessible chromatin regions, and found enrichment for transcription factor-binding motifs including SOX9 and FOS/JUN. For the first time, we have demonstrated the activity of OA-mQTLs and expression imbalance of OA effector genes during skeletogenesis. We show striking differences in the spatiotemporal function of these loci, contributing to our understanding of OA aetiology, with implications for the timing and strategy of pharmacological interventions.
2022-10-26 | GSE214394 | GEO
Project description:Background: Recent work identified and mapped a range of posttranscriptional modifications in mRNA, including methylation of the N6 and N1 positions in adenine, pseudouridylation and methylation of carbon 5 in cytosine (m5C). However, knowledge about prevalence and transcriptome-wide distribution of m5C is still extremely limited and thus, studies in different cell types, tissues and organisms are needed to gain insight into possible functions of this modification and interactions with other regulatory processes Results: We carried out an unbiased global analysis of m5C in total and nuclear poly(A)RNA of embryonic stem cells (ESCs) and brain of the mouse. We show that there are intriguing differences in these samples and cell compartments with respect to degree of methylation, functional classification of methylated transcripts and position bias within the transcript. Specifically, we observe a pronounced accumulation of m5C sites in the vicinity of the translational start codon, depletion in coding sequences and mixed patterns of enrichment in the 3’UTR. Degree and pattern of methylation distinguish transcripts modified in both ESCs and brain from those methylated in either one of the samples. Furthermore, we observed significant enrichment of m5C in the vicinity of the transcriptional start site in lncRNAs. We also present data regarding correlations between m5C and N6-methyladenosine, miRNA target sites and binding sites of RNA binding proteins. Conclusion: Our study presents the first comprehensive picture of cytosine methylation in the mouse epitranscriptome. These data can serve as a basis for future studies of function and biological significance of m5C in mRNA in mammals.
2016-12-09 | GSE83432 | GEO
Project description:5-methylcytosine (m5C) RNA modification installed by methyltransferase NSUN2 regulates gene expression and cell fate. Retinoblastoma (RB) is the most common primary intraocular tumor in children. However, the functional role of m5C modification in retinoblastoma remains unclear. Here, we show that 5-methylcytosine significantly promotes the progression of retinoblastoma. Retinoblastoma samples showed increased m5C levels, indicating a poor prognosis. Changes in global m5C modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, NSUN2 stabilized the methylated PFAS mRNA, a tumor promoter in retinoblastoma. Our work uncovers a critical function for m5C methylation in retinoblastoma and provides additional insight into the understanding of m5C modification.
2022-10-07 | GSE214685 | GEO
Project description:Cartilage destruction in osteoarthritis (OA) results from disturbed chondrocyte metabolism. Here, we used microarrays to show that TGF alpha and CCL2 are simultaneously upregulated in a rat model of OA and cooperate to drive cartilage degradation. The goals of the experiments included here were to a) characterize gene expression in knee joint articular chondrocytes at various stages of development of OA (2 and 8 weeks after surgical induction of OA), and b) to establish trends in gene expression among groups of genes related to the TGF alpha-EGFR axis, over time, in OA. The model chosen to study these results has been previously validated (Appleton, CT et al, 2007, Arthritis Rheum) and used to describe similar gene expression results at a different time point (4 weeks) after induction of OA. The rat model of OA involves surgical destabilization of the knee joint, followed by forced low-intensity mobilization over several weeks; a sham surgery is used as the control (representing a healthy non-OA knee joint) wherein a surgical incision is made but not structural (i.e. ligamentous) modification is made to the joint. Altogether, our data indicate that TGF and CCL2 cooperate to drive cartilage degradation in osteoarthritis. A total of 12 samples were analyzed. 3 replicates were used per condition: OA surgery at 2 weeks, OA surgery at 8 weeks, Sham (control) surgery at 2 weeks and Sham surgery at 8 weeks. Expression of OA samples was assessed relaitve to Sham (control) expression levels.
2012-11-15 | E-GEOD-42295 | biostudies-arrayexpress
Project description:Canine forms of osteoarthritis (OA) are very similar to those in humans and represent a welfare problem in the dog world population. In this study, we investigated the transcriptomic profile of peripheral blood in German Shepherd dogs with OA in order to identify diagnosis biomarkers. The bulk RNA-seq experiment was performed in a cohort of 12 adult dogs, 5 affected and 7 unaffected. Radiographs of the affected dogs revealed severe osteoarthritis in hip and elbow joints. The expression analysis showed 171 differentially expressed genes (DEGs), 113 were upregulated and 58 were downregulated compared to control dogs P (< 0.01). This pool of genes was functional annotated for signaling pathways using PANTHER tools. No overrepresented pathways were found. To gain further insights of the functional role of the DEGs in OA, we set a threshold of log2FoldChange value between -1.5 and 1.5. We ended up with 24 top up- and downregulated transcripts. Prioritization of these DEGs according to their known functional knowledge, revealed 5 possible candidates for OA biomarkers. The downregulated OSCAR gene encodes the osteoclast associated Ig-like receptor, which is involved in osteoclastogenesis regulation and bone homeostasis. In addition, the upregulated microRNA MIR339-1 and ncRNAs: LOC106559235 (downregulated), LOC102156762 (downregulated) and LOC111096460 (upregulated) are regulatory sequences, stable for gene profiling assessment in blood and related to OA pathogenesis regulation. We suggest OSCAR as the more likely candidate biomarker for OA diagnosis in dogs and, provide evidence of new circulating regulatory sequences differentially expressed in canine OA.
2021-12-22 | GSE191273 | GEO