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SRP114712
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Interplay between metabolic state of the cell and its ability to undergo immunological activation has been recently recognized as a treasure chest of novel fundamental regulatory principles. Itaconate, and its membrane permeable derivative dimethyl itaconate (DI) were recently shown to selectively inhibit subset of cytokines during macrophage activation (e.g. Il1b, il6, Il12b but not TNF), yet the precise mechanism of this effect remained unclear. We find that selectivity of DI action stems from the inhibitory effects of electrophilic stress exerted by DI on IkB-zeta protein translation, leading to selective control of the secondary wave of Nfkb-signaling. Mechanistically, DI leads to glutathione depletion and subsequent activation of both Nrf2-dependent and Nrf2-independent stress responses. We find that IkB-zeta regulation is carried out in Nrf2-independent manner, and identify Atf3 as a key mediator of DI effects on IkB-zeta/IL6. This inhibitory effect is conserved across species and cell types, as evident from inhibition of IkB-zeta production in activating human monocytes and IL-17A stimulated keratinocytes of both human and mice. Finally, DI administration in vivo ameliorated IL17/IkB-zeta-driven skin pathology in the mouse model of psoriasis, highlighting therapeutic potential of this regulatory pathway. Overall design: Bone marrow-derived macrophages (BMDMs) from WT and Nrf2–/– mice were derived in 7 days in MCSF supplemented complete RPMI. Some samples cells were stimulated with 250 uM DimethylItaconate(DI) for 12 hours prior to collection for RNA-seq.
Publication Title
Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Sugars modulate expression of hundreds of genes in plants. Previous studies on sugar signaling, using intact plants or plant tissues, were hampered by tissue heterogeneity, uneven sugar transport and/or inter-conversions of the applied sugars. This, in turn, could obscure the identity of a specific sugar that acts as a signal affecting expression of given gene in a given tissue or cell-type. To bypass those biases, we have developed a novel biological system, based on stem-cell-like Arabidopsis suspension culture. The cells were grown in a hormone-free medium and were sustained on xylose as the only carbon source. The functional genomics approach was used to identify sugar responsive genes, which rapidly (within 1 h) respond specifically to low concentration (1 mM) of glucose, fructose and/or sucrose.
Publication Title
Functional dissection of sugar signals affecting gene expression in Arabidopsis thaliana.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 46 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The goal of this study was to examine whether immune responses to Plasmodium chabaudi infection differ between the sexes and are altered by the presence of gonadal steroids. Gonadally-intact males were more likely than intact females to die following P. chabaudi infection, exhibit slower recovery from infection-associated weight loss, hypothermia, and anemia, have reduced IFN-associated gene expression and IFN production during peak parasitemia, and produce less antibody during the recovery phase of infection. Gonadectomy of male and female mice altered these sex-associated differences, suggesting that sex steroid hormone, in particular androgens and estrogens, may modulate immune responses to infection.
Publication Title
Involvement of gonadal steroids and gamma interferon in sex differences in response to blood-stage malaria infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng. Additional time points during transformation and activation were sequenced as well, but not assayed for expression.
Publication Title
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes
Publication Title
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genes differentially expressed in tumorigenic compared to non-tumorigenic, HPV18 positive cells
Publication Title
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to detail the global gene expression changes following RNAi knock-down of dTip60 in Drosophila SL2 cells
Publication Title
Widespread regulation of gene expression in the Drosophila genome by the histone acetyltransferase dTip60.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Despite initial and often dramatic responses of epidermal growth factor receptor (EGFR)-addicted lung tumors to the EGFR-specific tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, nearly all develop resistance and relapse. To explore novel mechanisms mediating acquired resistance, we employed non-small-cell lung cancer (NSCLC) cell lines bearing activating mutations in EGFR and rendered them resistant to EGFR-specific TKIs through chronic adaptation in tissue culture. In addition to previously observed resistance mechanisms including EGFR-T790M ''gate-keeper'' mutations and MET amplification, a subset of the seven chronically adapted NSCLC cell lines including HCC4006, HCC2279 and H1650 cells exhibited marked induction of fibroblast growth factor (FGF) 2 and FGF receptor 1 (FGFR1) mRNA and protein. Also, adaptation to EGFR-specific TKIs was accompanied by an epithelial to mesenchymal transition (EMT) as assessed by changes in CDH1, VIM, ZEB1 and ZEB2 expression and altered growth properties in Matrigel. In adapted cell lines exhibiting increased FGF2 and FGFR1 expression, measures of growth and signaling, but not EMT, were blocked by FGFR-specific TKIs, an FGF-ligand trap and FGFR1 silencing with RNAi. In parental HCC4006 cells, cell growth was strongly inhibited by gefitinib, although drug-resistant clones progress within 10 days. Combined treatment with gefitinib and AZD4547, an FGFR-specific TKI, prevented the outgrowth of drug-resistant clones. Thus, induction of FGF2 and FGFR1 following chronic adaptation to EGFR-specific TKIs provides a novel autocrine receptor tyrosine kinase-driven bypass pathway in a subset of lung cancer cell lines that are initially sensitive to EGFR-specific TKIs. The findings support FGFR-specific TKIs as potentially valuable additions to existing targeted therapeutic strategies with EGFR-specific TKIs to prevent or delay acquired resistance in EGFR-driven NSCLC. Overall design: Examination of mRNA levels in DMSO and gefitinib-resistant cultures of HCC4006 and HCC827. Each group has two replicates.
Publication Title
A mechanism of resistance to gefitinib mediated by cellular reprogramming and the acquisition of an FGF2-FGFR1 autocrine growth loop.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Conversely, metabolic signals such as redox state, NAD+/NADH and AMP/ADP ratios or heme feed back to and modulate circadian mechanisms to optimize energy utilization across the 24-hour cycle. We show that the signaling molecule carbon monoxide (CO) generated by rhythmic heme degradation is required for normal circadian rhythms as well as circadian metabolic outputs.
Publication Title
Reciprocal regulation of carbon monoxide metabolism and the circadian clock.
Sample Metadata Fields
Sex, Specimen part
View Samples