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GSE34297
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Gene expression in mice skin stimulated with 3 different cytokines
Publication Title
Thymic stromal lymphopoietin is up-regulated in the skin of patients with systemic sclerosis and induces profibrotic genes and intracellular signaling that overlap with those induced by interleukin-13 and transforming growth factor β.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 18 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial would cap over the amputation site by 12 hours post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were i.p. injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3 and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.
Publication Title
Regenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.
Sample Metadata Fields
Sex, Time
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
A gene expression profiling study was conducted in which skin biopsy samples were collected for RNA extraction and hybridization to microarrays from patients with moderate-to-severe psoriasis who participated in the phase 1, guselkumab first-in-human randomized, double-blind, placebo-controlled trial.
Publication Title
Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. The goal of this study was to evaluate the clinical activity and tolerability of multiple doses of SRT2104, a selective activator of SIRT1, in patients with moderate to severe psoriasis after day 84 of treatment. Forty patients were randomized 4:1 to three escalating doses of SRT2104 (250, 500, 1000 mg/d SRT2104 or placebo). Across all SRT2104 groups, 34.6% of patients (9 out of 26; 90% CI 18.0%-54.2%, p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84. To evaluate the changes in expression profile with treatment and to identify pathways involved in histological improvement, a subset of 22 Pre and Post treatment biopsies from 11 patients (4 Placebo, 7 Active Treatment) were hybridized to hgu133plus2 chips. Improvement in histology was associated with modulation of IL-17 and TNF-_ signaling pathways and keratinocyte differentiation target genes. Various studies suggest a crucial role of TNF_ and IL-17 in psoriasis pathogenesis and IL-17/TNF_ synergism induces a strong induction of differentially expressed genes in psoriasis, thus advocating a crucial role of IL-17/TNF_ combination in the molecular basis of disease (Chiricozzi et al., 2010). In the current study, broad scale gene expression profiling revealed that SRT2104 significantly reduced known IL-17 and TNF_ responsive genes including SERPINB4, S100A12, SERPINB3, kynu etc. even though the sample size for this analysis was small. One of the most highly modulated genes by SRT2104 included Kynu, a gene that regulates tryptophan metabolism, known to confer antibacterial effector functions (Daubener and MacKenzie, 1999). Interestingly kynu is part of the etanercept residual genomic profile that is not modulated by etanercept therapy even though clinical efficacy is achieved. Possibly, SRT2104 may be modulating the lipid barrier of the epidermis of psoriatic skin via modulation of keratinocyte diferentiation genes, which would be consistent with the observed improvement in skin histology. These results indicate a combinatorial effect of SRT2104 on TNF_, and IL-17 inflammatory signaling pathways and keratinocyte differentiation that could be a contributing factor towards improvement in clinical scores by the SIRT1 activator, SRT2104.
Publication Title
A Randomized, Placebo-Controlled Study of SRT2104, a SIRT1 Activator, in Patients with Moderate to Severe Psoriasis.
Sample Metadata Fields
Treatment, Subject, Time
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Exposures to dioxin, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a wide array of toxicities in vertebrates and is mostly considered to be mediated through the inappropriate activation of the aryl hydrocarbon receptor (Ahr) signaling pathway. Although transcriptional regulation by Ahr is widely studied, the molecular mechanisms responsible for the adverse outcomes after Ahr activation are largely unknown. To identify the important events downstream of AHR activation that play an actual role in the toxic responses, we employed the zebrafish caudal fin regeneration models since Ahr activation blocks the regenerative process. Zebrafish regenerate their caudal fins by an orchestrated progression of cell migration, differentiation and proliferation controlled by a multitude of signaling pathways. This complex process was exploited as an in vivo platform to identify cross talk between Ahr and other signaling pathways. Global genomic analysis was performed in the larval regenerating fin tissue after exposure to TCDD in order to identify genes differentially regulated after Ahr activation. Comparative toxicogenomic analysis revealed that both adult and larval fins respond to TCDD during regeneration with mis-expression of Wnt signaling pathway members and Wnt target genes.
Publication Title
Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We developed a method to convert gene expression signatures across the Illumina and Affymetrix platforms.
Publication Title
Cross-platform prediction of gene expression signatures.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 24 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Zebrafish have the remarkable ability to regenerate body parts including the heart, spinal cord and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage-larvae also possess the ability to regenerate the caudal fin. A comparative genomic analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of Retinoic acid (RA), as one of the highly induced genes across the three regeneration platforms.
Publication Title
Comparative expression profiling reveals an essential role for raldh2 in epimorphic regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Introduction:The purpose of this study is to provide athe first global transcriptomic profiling and systems analysis of BoNT-A treated muscle over a one year period. Microarray analysis was performed on rat TA muscle from 4 groups (n=4/group) at 1,4, 12 and 52 weeks after BoNT-A injection and saline injected rats at 12 weeks as control. Fold changes were computed at each time point with respect to control. Results: Dramatic transcriptional adaptation occurs at 1 week with a paradoxical increase in expression of slow and immature isoforms; increased expression of genes in competing pathways of repair and atrophy; impaired mitochondrial biogenesis and increased metal ion imbalance. ECM adaptations occurred at 4weeks to the basal lamina and fibrillar ECM. The muscle transcriptome returned to the unperturbed state 12 weeks post-injection. Conclusion: Transcriptional adaptations resemble denervated muscle albeit some differences. Overall gene expression, across time, correlates with the generally accepted BoNT-A time course.
Publication Title
Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina Genome Analyzer II
Description
The goal of the study was to compare gene expression of P0 wild-type and P0 Satb2-/- cortices. Total RNAs were isolated from P0 cortices dissected from wild-type and Satb2-/- mice (n=3 for each genotype), following Qiagen RNAeasy kit instruction.Sequence libraries were made following Illumina RNA TruSeq library preparation guide.The libaries were pair-end sequenced (50nt per end). Differentially expressed genes were identified by DESEQ. Overall design: Total RNAs were isolated from P0 cortices (3 control and 3 mutants), and sequenced on Illumina Genome Analyzer
Publication Title
Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaHiSeq2000
Description
ER:RAS-G12V expressing IMR90 cells were transduced with N1ICD-containing or control vectors before treatment with either 100nM 4-OHT or vehicle for 6 days leading to Notch-induced senescence (NIS), RAS-induced senescence (RIS) or combined Notch and Ras-induced senescence (RNIS). Overall design: IMR90 cells expressing a 4-hydroxytamoxifen (4-OHT) inducible estrogen receptor (ER)-coupled RAS-G12V (ER:RAS-G12V) were transduced with N1ICD-FLAG-containing (residues 1758-2556 of human NOTCH1, as per Capobianco et al, Mol Cell Biol, 1997) or control vector before treatment with either 100nM 4-OHT or vehicle for 6 days , leading to RAS-induced senescence (RIS), NOTCH-induced senescence (NIS) or combined Ras & NOTCH-induced senescence (RNIS). The total RNA was then analysed for transcriptional profiling using mRNA-sequencing. There were 6 (six) biological replicates for each experimental condition. Untreated, vector-transduced ER:RAS IMR90 cells were the control condition
Publication Title
NOTCH1 mediates a switch between two distinct secretomes during senescence.
Sample Metadata Fields
No sample metadata fields
View Samples