O-linked β-N-acetylglucosamine transferase plays an essential role in heart development through regulating angiopoietin-1
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ABSTRACT:
PROVIDER: PRJNA612518 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11305661.fastq.gz | Fastqsanger.gz | |||
| SRR11305662.fastq.gz | Fastqsanger.gz | |||
| SRR11305663.fastq.gz | Fastqsanger.gz | |||
| SRR11305665.fastq.gz | Fastqsanger.gz | |||
| SRR11305666.fastq.gz | Fastqsanger.gz |
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Project description:O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes post-translational modification of target proteins by introducing O-GlcNAc moiety on serine or threonine residues. OGT critically regulates various cellular functions in many cell types. However, its roles in hematopoietic stem and progenitor cells (HSPCs) are totally unknown. Here we report critical roles of OGT in homeostasis of HSPCs. Ogt is highly expressed in HSPCs and its disruption led to their rapid loss with increased reactive oxygen species and apoptosis. In particular, Ogt-deficient HSCs lost quiescence and showed severe defects in self-renewal and long-term repopulation capacities. Interestingly, Ogt-deficient HSCs accumulated defective mitochondria due to impaired mitophagy with decreased key mitophagy regulators, Pink1 and Bnip3, through dysregulation of host cell factor 1 (HCF1)-H3K4me3 pathway, and overexpression of Pink1 rescued impaired mitophagy and numbers of Ogt-deficient HSCs. In summary, our results revealed that OGT plays an essential role in HSC maintenance by assuring mitochondrial quality through mitophagy.
2020-12-09 | GSE116433 | GEO
Project description:Regulation of mitophagy by O-linked N-acetylglucosamine transferase is essential for hematopoietic stem cell maintenance
| PRJNA478507 | ENA
Project description:O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only enzyme catalyzing O-GlcNAcylation. Although it has been shown that OGT plays an essential role in maintaining postnatal heart function, its role in heart development remains unknown. Here we showed that loss of OGT in early fetal cardiomyocytes led to multiple heart developmental defects including hypertrabeculation, biventricular dilation, atrial septal defects, ventricular septal defects, and defects in coronary vessel development. In addition, RNA sequencing revealed that Angiopoietin-1, required within cardiomyocytes for both myocardial and coronary vessel development, was dramatically downregulated in cardiomyocyte-specific OGT knockout mouse hearts. In conclusion, our data demonstrated that OGT plays an essential role in regulating heart development through activating expression of cardiomyocyte Angiopoietin-1.
| S-EPMC7182263 | biostudies-literature
Project description:Using RNA sequencing we compared the transcriptome change between control and OGT knockout heart samples
2020-03-14 | GSE146962 | GEO
Project description:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. In C. elegans, three mutant strains(genotypes used: N2 (wild-type), ogt-1 (ok1474), oga-1 (ok1207), and pmk-1 (km25)) were treated with the human pathogen S. aureus (SA) or P. aeruginosa(PA) and OP50 (E. coli control) with three biological replications.
2015-05-01 | E-GEOD-53732 | biostudies-arrayexpress
Project description:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response.
2015-05-01 | GSE53732 | GEO
Project description:O-GlcNAcylation is the modification of serine and threonine residues with beta-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. To investigate the role of protein O-GlcNAcylation on intestinal homeostasis, we generated intestinal epithelial cell (IEC)-specific O-GlcNAc transferase (OGT) knockout in mice. The KO mice developed spontanous intestinal inflammation. To determine the underlying molecular mechanisms, we performed RNA sequencing of ileum and colon epithelial cells of wildtype and IEC-OGT KO mice.
2017-06-27 | GSE100473 | GEO
Project description:An X-chromosome exome sequencing analysis identified a mutation in O-GlcNAc transferase (OGT) (pL254F) in a family with X-linked intellectual disability (XLID). Affected patient lymohoblastoids exhibit decreased steady state OGT levels owing to an unstable protein compared to the unaffected, related male controls. Suprisingly, global O-GlcNAc levels remained remained unaltered. This prompted us to check the both protein and mRNA levels of the other cycling enzyme, O-GlcNAcase (OGA) which was also lowered. This implies that a compensation mechanism exists, however imperfect, owing to the disease state of the individuals. We performed glabal transcriptome analysis to assess any other changes in message between patients and controls. Our study highlights small differences in the global transcriptome of patient lymhoblastoids that have the L254F mutation in O-GlcNAc transferase when compared to familial controls using Illumina sequencing of total RNA
2016-02-25 | E-GEOD-74263 | biostudies-arrayexpress
Project description:ObjectiveO-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) catalyzes the addition of O-GlcNAc and GlcNAcylation has extensive crosstalk with phosphorylation to regulate signaling and transcription. Pig OGT is located near the region of chromosome X that affects follicle stimulating hormone level and testes size. The objective of this study was to find the variations of OGT between European and Chinese pigs.MethodsPigs were tested initially for polymorphism in OGT among European and Chinese pigs by polymerase chain reaction and sequencing at the U.S. Meat Animal Research Center (USMARC). The polymorphism was also determined in an independent population of pigs including European and Chinese Meishan (ME) breeds at the National Institute of Animal Science (NIAS, RDA, Korea).ResultsThe intron 20 of OGT from European and Chinese pigs was 514 and 233 bp, respectively, in the pigs tested initially. They included 1 White composite (WC) boar and 7 sows (2 Minzu×WC, 2 Duroc [DU]×WC, 2 ME×WC, 1 Fengzing×WC) at USMARC. The 281-bp difference was due to an inserted 276-bp element and GACTT in European pigs. When additional WC and ME boars, the grandparents that were used to generate the 1/2ME×1/2WC parents, and the 84 boars of 16 litters from mating of 1/2ME×1/2WC parents were analyzed, the breeds of origin of X chromosome quantitative trait locus (QTL) were confirmed. The polymorphism was determined in an independent population of pigs including DU, Landrace, Yorkshire, and ME breeds at NIAS. OGT was placed at position 67 cM on the chromosome X of the USMARC swine linkage map.ConclusionThere was complete concordance with the insertion in European pigs at USMARC and NIAS. This polymorphism could be a useful marker to identify the breed of origin of X chromosome QTL in pigs produced by crossbreeding Chinese and European pigs.
| S-EPMC5494481 | biostudies-literature
Project description:The failing heart is subject to elevated metabolic demands, adverse remodeling, chronic apoptosis, and ventricular dysfunction. The interplay among such pathologic changes is largely unknown. Several laboratories have identified a unique posttranslational modification that may have significant effects on cardiovascular function. The O-linked β-N-acetylglucosamine (O-GlcNAc) posttranslational modification (O-GlcNAcylation) integrates glucose metabolism with intracellular protein activity and localization. Because O-GlcNAc is derived from glucose, we hypothesized that altered O-GlcNAcylation would occur during heart failure and figure prominently in its pathophysiology. After 5 d of coronary ligation in WT mice, cardiac O-GlcNAc transferase (OGT; which adds O-GlcNAc to proteins) and levels of O-GlcNAcylation were significantly (P < 0.05) elevated in the surviving remote myocardium. We used inducible, cardiac myocyte-specific Cre recombinase transgenic mice crossed with loxP-flanked OGT mice to genetically delete cardiomyocyte OGT (cmOGT KO) and ascertain its role in the failing heart. After tamoxifen induction, cardiac O-GlcNAcylation of proteins and OGT levels were significantly reduced compared with WT, but not in other tissues. WT and cardiomyocyte OGT KO mice underwent nonreperfused coronary ligation and were followed for 4 wk. Although OGT deletion caused no functional change in sham-operated mice, OGT deletion in infarcted mice significantly exacerbated cardiac dysfunction compared with WT. These data provide keen insights into the pathophysiology of the failing heart and illuminate a previously unrecognized point of integration between metabolism and cardiac function in the failing heart.
| S-EPMC2955091 | biostudies-literature