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GSE45867
Homo sapiens
36 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that is characterized by the presence of inflammatory cytokines, including interleukin-6 (IL-6). Here, we investigated the global molecular effects of Tocilizumab, an approved humanized anti-IL6 Receptor antibody, versus Methotrexate therapy, in synovial biopsy samples collected prospectively in early RA before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients.
Publication Title
Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: Rituximab displays therapeutic benefits in the treatment of rheumatoid arthritis (RA) patients resistant to TNF blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. In this study we investigated the global molecular effects of rituximab in synovial biopsies obtained from anti-TNF resistant RA patients before and after administration of the drug.
Publication Title
Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TNF antagonists are routinely used in severe rheumatoid arthritis (RA) patients who failed conventional DMARD therapy. According to large clinical trials, the three available drugs (adalimumab, infliximab and etanercept) display similar effects in terms of efficacy, tolerability and side effects. These studies also indicate that about 25% of RA patients treated with TNF-antagonists do not display any significant clinical improvement.
Publication Title
Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TNFalpha and IL1beta play a pathogenic role in rheumatoid arthritis. Both cytokines are known to activate cytokine and metalloproteinase secretion by synovial fibroblasts. In the present study, we wanted to investigate whether TNFalpha and IL1beta displayed differential effects on cultured Fibroblast-like Synovial Cells derived from RA patients. Global gene expression analyses indicated that both cytokines induced similar genes in these cells.
Publication Title
Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Maternal Embryonic Leucine Zipper Kinase (MELK), a Ser/Thr protein kinase, is highly over expressed in stem and cancer cells. The oncogenic role of MELK is attributed to its capacity to disable critical cell cycle checkpoints and to enhance replication. Most functional studies have relied on the use of siRNA/shRNA-mediated gene silencing, but this is often compromised by off target effects. Here we present the cellular validation of a novel, potent and selective small molecule MELK inhibitor, MELK-T1, which has enabled us to explore the biological function of MELK. Strikingly, the binding of MELK-T1 to endogenous MELK triggers a rapid and proteasome dependent degradation of the MELK protein. Treatment of MCF-7 breast adenocarcinoma cells with MELK-T1 leads to an accumulation of stalled replication forks and double strand breaks, followed by a replicative senescence phenotype. This phenotype correlates with a rapid and long-lasting ATM activation and phosphorylation of CHK2. Furthermore, MELK-T1 induces strong phosphorylation of p53 and prolonged up-regulation of p21.
Publication Title
MELK-T1, a small-molecule inhibitor of protein kinase MELK, decreases DNA-damage tolerance in proliferating cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
NextSeq 500
Description
This study aimed to explore the role of NIPP1 in adult germline cell proliferation and differentiation, using a ubiquitous inducible NIPP1 knockout (TKO) mouse model. To gain unbiased insight into the molecular mechanism that underly the sertoli-only phenotype in TKO, we performed a comparative RNA sequencing profiling of control and TKO, in which NIPP1 was tamoxifin-induced depleted. Overall design: Two genotypes are compared after treatment with tamoxifen. The control genotype (UBC CRE-ERT2+/- Ppp1r8 fl/+) looses the floxed allele of PPP1R8 (aka NIPP1) as a consequence of the treatment with tamoxifen and becomes heterozygous for PPP1R8. The KO genotype (UBC CRE-ERT2+/- Ppp1r8 fl/-) also looses the floxed allele of PPP1R8 as a consequence of the tamoxifen treatment and becomes homozygous KO. For each genotype, 4 replicates are profiled.
Publication Title
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found that Hopx is required for the function of DC-induced regulatory T cells in vivo. We used microarrays to identify relevant Hopx-targets in such cells after antigenic re-challenge in vivo.
Publication Title
The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
Sparse populations of neurons in the dentate gyrus (DG) of the hippocampus are causally implicated in the encoding of contextual fear memories. However, engram-specific molecular mechanisms underlying memory consolidation remain largely unknown. Here we perform unbiased RNA sequencing of DG engram neurons 24h after contextual fear conditioning to identify transcriptome changes specific to memory consolidation. DG engram neurons exhibit a highly distinct pattern of gene expression, in which CREB-dependent transcription features prominently (P=6.2x10-13), including Atf3 (P=2.4x10-41), Penk (P=1.3x10-15), and Kcnq3 (P=3.1x10-12). Moreover, we validate the functional relevance of the RNAseq findings by establishing the causal requirement of intact CREB function specifically within the DG engram during memory consolidation, and identify a novel group of CREB target genes involved in the encoding of long-term memory. Overall design: Biological replicates: Fear conditioned: n=14, No shock controls: n=4, Home cage controls:n=3. The contents 10 dVenus+ and 10 dVenus- cells were aspirated from each animal (biological replicate)
Publication Title
Engram-specific transcriptome profiling of contextual memory consolidation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- NextSeq 500
Description
The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury. Overall design: We generated transciptome data from proliferative cardiac cells collected from 3, 7 or 14 days following myocardial infarction (MI) or sham surgery. This series includes single-cell transcriptome data from (Ki67-RFP+) cardiac cells collected from neonatal murine hearts, adult homeostatic murine hearts or adult murine hearts collected 14 days following myocardial infarction (MI), ischemic/perfusion (I/R) or sham surgery.
Publication Title
Profiling proliferative cells and their progeny in damaged murine hearts.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 156 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of NSCLC. A prognostic signature of 17 genes showed the best association with post-surgery survival time. The performance of the signatures was validated using a patient cohort of similar size
Publication Title
Gene expression-based classification of non-small cell lung carcinomas and survival prediction.
Sample Metadata Fields
Sex, Specimen part
View Samples