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GSE89731
Caenorhabditis elegans
6 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction regimens lead to enhanced stress resistance and extended lifespan in many species through the regulation of fasting and/or diet responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Several studies have implicated that the nervous system is involved in the regulation of longevity. However, it remains largely unknown whether the nervous system contributes to the regulation of lifespan and/or stress resistance elicited by fasting. In this study, we first investigated the role of the nervous system in fasting-elicited longevity and stress resistance. We found that lifespan extension in Caenorhabditis elegans caused by an intermittent fasting (IF) regimen was suppressed by functional defects in sensory neurons. The IF-induced longevity was also suppressed in a mutant that lacks the enzyme required for the synthesis of an amine neurotransmitter, octopamine (OA), which acts in the absence of food, i.e., under fasting conditions. Although OA administration did not significantly extend the lifespan, it enhanced organismal resistance to oxidative stress. This enhanced resistance was suppressed by a mutation of the OA receptors, SER-3 and SER-6. Moreover, we found that OA administration promoted the nuclear translocation of DAF-16, the key transcription factor in fasting responses, and that the OA-induced enhancement of stress resistance required DAF-16. Altogether, our results suggest that OA signaling, which is triggered by the absence of food, shifts the organismal state to a more protective one to prepare for environmental stresses.
Publication Title
Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To analyse roles of HAI-1/Spint1 in intestinal tumorigenesis, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods.
Publication Title
Hepatocyte growth factor activator inhibitor type 1 is a suppressor of intestinal tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 46 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction extends lifespan and delays the age-related physiological decline in many species. Intermittent fasting (IF) is one of the most effective dietary restriction regimens that extends lifespan in C. elegans and mammals1,2. In C. elegans, the FOXO transcription factor DAF-16 is implicated in fasting-induced gene expression changes and the longevity response to IF3; however, the mechanisms that sense and transduce fasting-stress stimuli have remained largely unknown. Here we show that a KGB-1/AP1 (activator protein 1) module is a key signalling pathway that mediates fasting-induced transcriptional changes and IF-induced longevity. Our promoter analysis coupled to genome-wide microarray results has shown that the AP-1-binding site, together with the FOXO-binding site, is highly over-represented in the promoter regions of fasting-induced genes. We find that JUN-1 (C. elegans c-Jun) and FOS-1 (C. elegans c-Fos), which constitute the AP-1 transcription factor complex, are required for IF-induced longevity. We also find that KGB-1 acts as a direct activator of JUN-1 and FOS-1, is activated in response to fasting, and, among the three C. elegans JNKs, is specifically required for IF-induced longevity. Our results demonstrate that most fasting-induced upregulated genes, including almost all of the DAF-16-dependent genes, require KGB-1 and JUN-1 function for their induction, and that the loss of kgb-1 suppresses the fasting-induced upregulation of DAF-16 target genes without affecting fasting-induced DAF-16 nuclear translocation. These findings identify the evolutionarily conserved JNK/AP-1 module as a key mediator of fasting-stress responses, and suggest a model in which two fasting-induced signalling pathways leading to DAF-16 nuclear translocation and KGB-1/AP-1 activation, respectively, integrate in the nucleus to coordinately mediate fasting-induced transcriptional changes and IF-induced longevity.
Publication Title
A fasting-responsive signaling pathway that extends life span in C. elegans.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Intermittent fasting is one of the most effective dietary restriction regimens that extend life-span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce fasting-stimulus have remained largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we have found that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acted as an activator of AP-1, and was activated in response to fasting. KGB-1 and AP-1 were involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhanced protein ubiquitination, and reduced protein carbonylation. Our results have thus identified a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity partly through regulating proteostasis.
Publication Title
A fasting-responsive signaling pathway that extends life span in C. elegans.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: To determine the effects of age and topographic location on gene expression in human neural retina.
Publication Title
Effects of aging and anatomic location on gene expression in human retina.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: The goal of this study was to determine biological consequences during liver regeneration following partial hepatectomy in mice by next-generation sequencing. A particular interest was to compare mice with either a floxed b-PDGFR allele to mice that harbored a deletion of b-PDGFR in hepatic stellate cells (HSCs), by crossing b-PDGFR fl/fl mice with transgenic GFAP-Cre mice. Methods: b-PDGFR fl/fl mice or mice with a HSC-specific deletion of b-PDGFR underwent either sham operation or 70% partial hepatectomy. Following 72 hours, livers were collected and total RNA was extracted using tizol, followed by a purification using Quiagen spin columns including an on-column DNAse digestion step. Conclusion: Our study represents a detailed analysis of hepatic transcriptome, with biologic replicates, generated by RNA-seq technology of livers following sham operation or partial hepatectomy in b-PDGFR fl/fl mice or b-PDGFRfl/fl/GRAP-Cre mice. Overall design: Whole liver mRNA profiles of sham operated livers or livers collected 72hours after partial hepatectomy of beta-PDGFR fl/fl and beta-PDGFR fl/fl/GFAP-Cre (creating a hepatic stellate cell-specific deletion of b-PDGFR) mice were generated by deep sequencing, in duplicate, using Illumina HiSeq2000.
Publication Title
Induction and contribution of beta platelet-derived growth factor signalling by hepatic stellate cells to liver regeneration after partial hepatectomy in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 7 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Although an appropriate range of fluoride is thought to be safe and effective, excessive fluoride intake results in toxic effects in either hard tissues of teeth and skeleton or soft tissues of kidney, lung and brain. It is also well known that fluoride at a millimolar range elicits the complex cellular responses such as enzyme activity, signal transduction and apoptosis in many kinds of cells. However, its toxic effects are still unclear.
Publication Title
Genes and gene networks involved in sodium fluoride-elicited cell death accompanying endoplasmic reticulum stress in oral epithelial cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells express different sets of receptor type tyrosine kinases. These receptor kinases may be activated through autocrine or paracrine mechanisms. Fibroblasts may modify the biologic properties of surrounding cancer cells through paracrine mechansms.
Publication Title
The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 4 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
UHRF1 (Ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 to hemimethylated DNA during replication, is essential for maintaining DNA methylation patterns during cell division and is suggested to direct additional repressive epigenetic marks. Uhrf1 mutation in zebrafish results in multiple embryonic defects including failed hepatic outgrowth, but the epigenetic basis of these phenotypes is not known. We find that DNA methylation is the only epigenetic mark that is depleted in uhrf1 mutants and make the surprising finding that despite the reduced organ size in uhrf1 mutants, genes regulating DNA replication and S-phase progression were highly upregulated. Further, there is a striking increase in BrdU incorporation in uhrf1 mutant cells, and they retained BrdU labeling over several days, indicating they are arrested in S-phase. Moreover, some of the label retaining nuclei co-localized with TUNEL positive nuclei, suggesting that arrested cells are responsible for apoptosis. Importantly, dnmt1 mutation phenocopies the S-phase arrest and hepatic outgrowth defects in uhrf1 mutants and Dnmt1 knock-down enhances the uhrf1 hepatic phenotype. Together, these data indicate that DNA hypomethylation is sufficient to generate the uhrf1 mutant phenotype by promoting an S-phase arrest. We thus propose that cell cycle arrest is a mechanism to restrict propagation of epigenetically deranged cells during embryogenesis.
Publication Title
DNA hypomethylation induces a DNA replication-associated cell cycle arrest to block hepatic outgrowth in uhrf1 mutant zebrafish embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to find the difference between human lung tissue-derived fibroblasts and human vascular adventitial fibroblasts for enhancing tumor formation ablity of human lung adenocarcinoma cell line A549, we found that human vascular adventitial fibroblasts enhance A549 tumor formation in vivo compared to human lung tissue-derived fibroblasts. To find the responsible genes for this phenomena, we used microarray analysis to find the expression difference between lung tissue-derived fibroblasts and vascular adventitial fibroblas
Publication Title
Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation: podoplanin in fibroblast functions for tumor progression.
Sample Metadata Fields
Specimen part
View Samples