Expression profile by RNA-seq of wild type or Caenorhabditis elegans mutant for the Werner syndrome gene ortholog treated with or without vitamin C
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ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE54173 | GEO | 2014/10/07
SECONDARY ACCESSION(S): PRJNA235332
REPOSITORIES: GEO
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Project description:In this study, we analyzed the impact of a mutation in the wrn-1 gene compared to wild type worms and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology. Whole C. elegans mRNA profiles at the L4 stage of wild type and wrn-1(gk99) mutant animals treated with or without 10 mM ascorbate were generated by deep sequencing, in triplicate, using the HiSeq 2000 machine form Illumina. Detailed statistics on the quality of the reads were calculated with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). The 50 base pairs raw sequences were aligned on the C. elegans ce10/W220 genome with TopHat using the Ensembl annotations provided with the Illumina iGenomes. The htseq-count software (http://www-huber.embl.de/users/anders/HTSeq) was used to count the number of reads aligned to each gene. These counts were then normalized relative to the sequencing depth with DESeq.
2014-10-07 | E-GEOD-54173 | biostudies-arrayexpress
Project description:We investigated whether dietary vitamin D supplementation can rescue the expression of genes that are dysregulated within the neocortex of Mecp2+/- mice, and whether vitamin D deficiency further exacerbates transcriptome disruptions in these mice. We found that dietary vitamin D modification has a profound impact on the transcriptome of the neocortex. We identified more than 200 differentially expressed genes whose expression is normalized with vitamin D supplementation, many of which are associated with neuronal morphology. Dietary vitamin D deficiency exacerbated the dysregulation of many of these genes in the Mecp2+/- cortex, but, strikingly, it normalized the expression of many other dysregulated genes, similar to the effect of supplementation.
2022-01-31 | GSE180630 | GEO
Project description:BackgroundWerner Syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS encodes a DNA helicase/exonuclease protein believed to affect different aspects of transcription, replication, and DNA repair. Caenorhabditis elegans (C. elegans) with a nonfunctional wrn-1 DNA helicase ortholog also exhibits a shorter life span, which can be rescued by vitamin C. In this study, we analyzed the impact of a mutation in the wrn-1 gene and the dietary supplementation of vitamin C on the global mRNA expression of the whole C. elegans by the RNA-seq technology.ResultsVitamin C increased the mean life span of the wrn-1(gk99) mutant and the N2 wild type strains at 25°C. However, the alteration of gene expression by vitamin C is different between wrn-1(gk99) and wild type strains. We observed alteration in the expression of 1522 genes in wrn-1(gk99) worms compared to wild type animals. Such genes significantly affected the metabolism of lipid, cellular ketone, organic acid, and carboxylic acids. Vitamin C, in return, altered the expression of genes in wrn-1(gk99) worms involved in locomotion and anatomical structure development. Proteolysis was the only biological process significantly affected by vitamin C in wild type worms.ConclusionsExpression profiling of wrn-1(gk99) worms revealed a very different response to the addition of vitamin C compared to wild type worms. Finally, vitamin C extended the life span of wrn-1(gk99) animals by altering biological processes involved mainly in locomotion and anatomical structure development.
| S-EPMC4221712 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series:; GSE8146: Age-related transcriptional changes and the effect of dietary supplementation of vitamin E in the mouse heart; GSE8150: Age-related transcriptional changes and the effect of dietary supplementation of vitamin E in the mouse brain Experiment Overall Design: Refer to individual Series
2008-06-16 | E-GEOD-8162 | biostudies-arrayexpress
Project description:Werner syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS is believed to be involved in different aspects of transcription, replication, and/or DNA repair. We generated a mouse model with a deletion in the helicase domain of the murine WRN homologue that recapitulates most of the WS phenotypes including an abnormal hyaluronic acid excretion, higher reactive oxygen species (ROS) levels, increased genomic instability and cancer incidence resulting in a 10-15% decreased life span expectancy. In addition, WS patients and Wrn mutant mice show hallmarks of a metabolic syndrome including premature visceral obesity, hypertriglyceridemia, insulin-resistant diabetes type 2 and associated cardiovascular diseases. In this study, we compared the expression profile of liver tissues from 9 months old Wrn mutant and wild type animals. Gene set enrichment analysis of the microarray data indicated that Wrn mutant mice exhibited down-regulation of genes normally decreased in several transgenic mouse models of hepatoma and during caloric restriction. Wrn mutant mice also altered the expression of genes involved in inflammation as well as in glutathione and xenobiotic metabolisms. These results indicate that Wrn mutant mice respond to the observed oxidative stress by altering the necessary pathways to survive. Vitamin C supplementation rescued the life span expectancy of Wrn mutant mice and reversed several age-related abnormalities in adipose, cardiac, and liver tissues, genomic integrity and inflammatory status. Finally, gene set enrichment analyses revealed that vitamin C decreased genes normally up regulated in human WS fibroblasts and cancers and it increased genes involved in tissue injury response and adipocyte dedifferentiation in obese mice. Experiment Overall Design: Microarray analyses were performed on the liver tissues of 9 months old mice. Four independent biological replicates of this experiment (wild type vs Wrn mutant or wild type vs vitamin C treated mutant mice) were carried out with a dye swap on two replicates of each genotype.
2009-09-11 | E-GEOD-14549 | biostudies-arrayexpress
Project description:Metabolic dysfunction is one of the main symptoms of Werner syndrome (WS); however, the underlying mechanisms remain unclear. Here, we report that loss of WRN accelerates adipogenesis at an early stage both in vitro (stem cells) and in vivo (zebrafish). Moreover, WRN depletion causes a transient upregulation of late-stage of adipocyte-specific genes at an early stage.
2024-01-26 | GSE248012 | GEO
Project description:Werner syndrome (WS) is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. We used microarrays to examine whether global gene expression profile of WS iPSCs is similar to that of normal iPSCs and human ESCs, as well as premature senescence phenotype is suppressed by reprogramming.
2014-12-31 | GSE62114 | GEO
Project description:Werner syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS is believed to be involved in different aspects of transcription, replication, and/or DNA repair. The poly(ADP-ribose) polymerase-1 (PARP-1) enzyme is also involved in DNA repair and is known to affect transcription of several genes. In this study, we examined the expression profile of cells lacking the normal function of either or both enzymes. All mutant cells exhibited altered expression of genes normally responding to oxidative stress. Interestingly, more than 58% of misregulated genes identified in double mutant cells were not altered in cells with either the Wrn or PARP-1 mutation alone. Consequently, the impact on gene expression profile when both Wrn and PARP-1 are mutated was greater than a simple addition of individual mutant genotype. In addition, double mutant cultured cells showed major misregulation of genes involved in apoptosis, cell cycle control, embryonic development, metabolism, and signal transduction. More importantly, in vivo analyses of double mutant mice have confirmed the increased apoptosis and the developmental defects in embryos as well as the major increase in intracellular phosphorylation and oxidative DNA damage in adult tissues. They also exhibited a progressive increase in oxidative stress with age. Thus, a major result of this study is that changes in expression of several genes and physiological functions identified in vitro were confirmed in mouse embryonic and adult tissues. Experiment Overall Design: Microarray analyses were performed on cell cultures at the second passage (10 population doublings). For each genotype, asynchronously dividing cells derived from three healthy 15.5 day embryos from one litter were pooled at the second passage and cytoplasmic RNA was extracted. Cytoplasmic RNA was used in these experiments to avoid contamination with heterogeneous nuclear RNA and genomic DNA. (Note that DNAse treatment was also applied to all samples). This pool of RNA was labeled sample number 1 for each genotype. Pooling of embryonic cells was performed to minimize the effect of inter-individual biological differences. A second pool of embryonic cells was also created from a separate dam (second litter) for each genotype (called samples number 2). This strategy allowed obtaining samples in duplicate for each genotype. The cRNA from wild type cells were synthesized with Cy-5 labeled nucleotides and cRNAs from Wrn mutant, PARP-1 null, and PARP-1 null/Wrn mutant cells were synthesized with Cy-3 labeled nucleotides. Hybridization was performed on Mouse Agilent 60-mer Oligo Microarray chips by mixing wild type labeled cRNA (baseline expression levels) with either Wrn mutant, PARP-1 null, or PARP-1 null/Wrn mutant cRNA. Hybridization experiments were done in duplicates.
2008-06-12 | E-GEOD-3359 | biostudies-arrayexpress
Project description:Our data throw light upon the effect of WRN deficiency on gene expression and epigenomic modification, which indicates aging-associated changes from both genomic and epigenomic level. It was compared between WRN+/+ and WRN-/- in hESCs and hMSCs that the gene expression landscapes and epigenetic modifications(H3K4me3, H3K27me3, H3K9me3 and 5-methylcytosine).
2015-05-13 | E-GEOD-52285 | biostudies-arrayexpress
Project description:Werner syndrome (WS) is a rare disorder characterized by the premature onset of a number of age-related diseases. The gene responsible for WS is believed to be involved in different aspects of transcription, replication, and/or DNA repair. We generated a mouse model with a deletion in the helicase domain of the murine WRN homologue that recapitulates most of the WS phenotypes including an abnormal hyaluronic acid excretion, higher reactive oxygen species (ROS) levels, increased genomic instability and cancer incidence resulting in a 10-15% decreased life span expectancy. In addition, WS patients and Wrn mutant mice show hallmarks of a metabolic syndrome including premature visceral obesity, hypertriglyceridemia, insulin-resistant diabetes type 2 and associated cardiovascular diseases. In this study, we compared the expression profile of liver tissues from 9 months old Wrn mutant and wild type animals. Gene set enrichment analysis of the microarray data indicated that Wrn mutant mice exhibited down-regulation of genes normally decreased in several transgenic mouse models of hepatoma and during caloric restriction. Wrn mutant mice also altered the expression of genes involved in inflammation as well as in glutathione and xenobiotic metabolisms. These results indicate that Wrn mutant mice respond to the observed oxidative stress by altering the necessary pathways to survive. Vitamin C supplementation rescued the life span expectancy of Wrn mutant mice and reversed several age-related abnormalities in adipose, cardiac, and liver tissues, genomic integrity and inflammatory status. Finally, gene set enrichment analyses revealed that vitamin C decreased genes normally up regulated in human WS fibroblasts and cancers and it increased genes involved in tissue injury response and adipocyte dedifferentiation in obese mice.
2009-09-08 | GSE14549 | GEO