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GSE51440
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- 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- 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- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
ER:RAS-G12V expressing IMR90 cells were treated with either 100nM 4-OHT for 6 days or 100uM Etoposide for 2 days, followed by further culture for 5 days, leading to RAS-induced senescence (RIS) and DNA-damage induced senescence (DDIS) respectively. Overall design: IMR90 cells expressing a 4-hydroxytamoxifen (4-OHT) inducible estrogen receptor (ER)-coupled RAS-G12V (ER:RAS-G12V) were treated with either 100nM 4-OHT for 6 days or 100uM Etoposide for 2 days, followed by further culture for 5 days, leading to RAS-induced senescence (RIS) and DNA-damage induced senescence (DDIS) respectively. The total RNA was then analysed for transcriptional profiling using mRNA-sequencing. There were 8 (eight) biological replicatesfor each of the experimental conditions. Untreated 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- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF:huex10stv2_57_37b_0112.cdf (huex10st)
Description
Glucocorticoids (GC) are pivotal in the treatment of childhood acute lymphoblastic leukaemia (ALL) but resistance is a continuing clinical problem with the underlying mechanisms still unclear. An isobaric tag proteomic approach was used to compare protein profiles of the B lineage ALL GC-sensitive cell line, PreB 697, and its GC-resistant sub-line, R3F9, before and after dexamethasone exposure. Two transcription factors involved in B- cell differentiation, PAX5 and IRF4, were differentially regulated in the PreB 697 compared to the R3F9 cell line in response to GC. PAX5 basal protein expression was less in R3F9 compared to its GC-sensitive parent and was confirmed to be lower in other GC-resistant sub-lines of Pre B697 and was associated with a decreased expression of the PAX5 transcriptional target, CD19. Gene set enrichment analysis of microarray data from the cell lines showed that increasing GC-resistance was associated with differentiation from preB-II to an immature B-lymphocytes stage. GC resistant sub lines were shown to have a higher levels of p-JNK compared to the parent line and JNK inhibition caused re-sensitisation to GC. Reduced CD19 levels accompanying GC resistance was also apparent in some clinical samples, with high levels of MRD persisting after GC containing induction chemotherapy. Thus, quantitative proteomic analysis reveals a role for PAX5 and maturation as a recurrent mechanism underlying glucocorticoid resistance in ALL and identifies JNK inhibitors as a possible re-sensitising therapy.
Publication Title
Quantitative proteomic analysis reveals maturation as a mechanism underlying glucocorticoid resistance in B lineage ALL and re-sensitization by JNK inhibition.
Sample Metadata Fields
No sample metadata fields
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- 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
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