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GSE25295
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Clinically significant radiation-induced lung injury (RILI) is associated with significant morbidity and mortality and a common toxicity in patients administered thoracic radiotherapy. While the molecular etiology of RILI is poorly understood, we previously characterized a murine model of RILI in which alterations in lung endothelial barrier integrity surfaced as a potentially important pathobiologic event. In these studies, inhibition of HMG-CoA reductase activity (simvastatin) reduced murine RILI-associated lung inflammation and vascular leak and attenuated radiation-induced dysregulation of sphingolipid metabolic pathway genes identified by genome-wide lung gene expression profiling. In the present study, we test the hypothesis that sphingolipid signaling components serve as important modulators of RILI pathobiology and novel therapeutic targets. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to cumulative sphingosine-1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue following 25 Gy exposure (6 weeks). Moreover, genetically-engineered mice with either targeted deletion of SphK1 (SphK1-/-), or with reduced expression of selective members of the S1P receptor family (S1PR1+/-, S1PR2-/-, S1PR3-/-,), exhibited marked susceptibility to RILI-mediated lung inflammation. Finally, we assessed the efficacy of three potent vascular barrier-protective S1P analogues FTY720 (FTY), fTysiponate (fTyS) and SEW-2871 (SEW) in attenuating indices of RILI. The phosphonate analogue, fTyS, and to a lesser degree SEW, exhibited significant attenuation of RILI and RILI-induced gene dysregulation compared to control RILI-challenged mice (6 weeks). In contrast, FTY failed to significantly alter physiologic or genomic changes compared to RILI-challenged controls. Together, these results support the targeting of sphingolipid components as a novel and effective therapeutic strategy in RILI.
Publication Title
Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus, Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TR subtype versus TR, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TR, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TR to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare.
Publication Title
Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We performed microarray analysis in order to evaluate the combination effect of the mitochondrial matrix chaperone inhibitor gamitrinib-triphenylphosphonium (G-TPP) and Liver X receptor agonist LXR623 on gene expression in stem cell like glioma cells (NCH644).
Publication Title
Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Quiescent stem cells are periodically activated to maintain tissue homeostasis or occasionally called into action upon injury. Molecular mechanisms that constitutively maintain stem cell identity or promote stem cell proliferation and differentiation upon activation have been extensively studied. However, it is unclear how quiescent stem cells maintain identity and reinforce quiescence when they transition from quiescence to activation. Here we show mouse hair follicle stem cell compartment induces a transcription factor, Foxc1, when activated. Importantly, deletion of Foxc1 in the activated but not quiescent stem cells compromises stem cell identity, fails to re-establish quiescence and subsequently drives premature stem cell activation.These findings uncover a dynamic, cell-intrinsic mechanism employed by hair follicle stem cells to reinforce stemness in response to activation. Overall design: Poly(A)-enriched transcriptome RNA-seq on HFSCs isolated in WT and K14Cre cKO mice at anagen and early telogen stage of hair cycle.
Publication Title
Foxc1 reinforces quiescence in self-renewing hair follicle stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina HiSeq 2000
Description
To assess the effect of different forms of TL1A within different organs of the mouse we generated 2 different transgenic mouse lines where TL1A was expressed under the control of the CD2 promoter. 2 forms of TL1A was used. Either WT TL1A, which led to over expression of both membrane bound and soluble forms of TL1A (Refered to as Mem+Sol) or TL1A Delta 69-93 which only overexpressed membrane restricted TL1A (Refered to as Mem). Lungs and terminal ileums were taken from Either Mem, Mem+sol or WT litermate control mice at 12 weeks of age and the transcriptome assessed using RNAseq Through this we demonstrated enrichment of different transcripts and pathways both dependent on and independent of the form of TL1A and the site of action. This study is also the first to use RNASeq to assess the resualt of overexpression of TL1A within the mouse. Overall design: Poly-A purified mRNA profiles from the Ileum and Lung of Mem, Mem+Sol and WT mice generated using Illumina based RNASeq
Publication Title
Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive Immune Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcriptional profiling of guard cells and mesophyll cells in response to ABA treatment
Publication Title
Isolation of a strong Arabidopsis guard cell promoter and its potential as a research tool.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Compound
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
U87 cells were transduced with IDH1 WT or IDH1 R132H and stable clones were selected.
Publication Title
Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Isolation and characterization of tumourigenic colon cancer initiating cells may help to develop novel diagnostic and therapeutic procedures. Methods: We characterized a panel of fourteen human colon carcinoma cell lines and their corresponding xenografts for the surface expression of different potential stem cell markers: CD133, CD24, CD44, CDCP1 and CXCR4. In five cell lines and nine xenografts mRNA expression of the investigated markers was determined. Tumour growth behaviour of CD133+, CD133- and unsorted SW620 cells was evaluated in vivo. Results: All surface markers showed distinct expression patterns in the examined tumours. Analyses of the corresponding xenografts revealed a significant reduction of cell numbers expressing the investigated markers. CD44 and CXCR4 mRNA expression correlated within the cell line panel and CD44 and CDCP1 within the xenograft panel, respectively. Small subpopulations of double and triple positive cells could be described. SW620 showed significantly higher take rates and shorter doubling times in vivo when sorted for CD133 positivity. Conclusion: Our data support the hypothesis of a small subset of cells with stem cell-like properties characterized by a distinct surface marker profile. In vivo growth kinetics give strong relevance for an important role of CD133 within the mentioned surface marker profile.
Publication Title
Characterization of colon cancer cells: a functional approach characterizing CD133 as a potential stem cell marker.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
We identified Ncoa3 as a regulator of neuronal morphology and microRNA activity. In order to uncover target genes of this transcriptional coactivator we performed this microarray analysis.
Publication Title
A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function.
Sample Metadata Fields
Specimen part, Treatment
View Samples