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SRP058850
Mus musculus
6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Aim: To determine the role of NOTCH during the response-to-injury and subsequent chronic inflammatory process of the arterial wall underlying atherosclerosis. Methods and results: We have generated an endothelial-specific RBPJK depleted mice using the Cdh5 cadherin promoter (ApoE-/-;RBPJflox/flox;Cdh5- CreERT). Endothelial-specific deletion of the Notch effector RBPJK or systemic deletion of the Notch1 receptor in athero-susceptible ApoE-/- mice fed a HC diet for 6 weeks resulted in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy revealed decreased leukocyte rolling on the endothelium of ApoE-/-;RBPJflox/flox;Cdh5- CreERT, that correlated with the lesser presence of leukocyts and macrophages in the vascular wall. Consistent with this, transcriptome analysis revealed that proinflammatory and endothelial activation pathways were downregulated in atherosclerotic tissue of RBPJk-mutant mice.. Jagged1 signaling upregulation in endothelial cells promotes the physical interaction and nuclear translocation of the intracellular domain of the Notch1 receptor (N1ICD) with NF-kB,. This N1ICD and NF-kB interaction is required for reciprocal transactivation of target genes including vascular cell adhesion molecule-1 (Vcam1). Conclusions: Notch signaling pathway inactivation decreases leukocyte rolling, thereby preventing endothelial dysfunction and vascular inflammation. Thus attenuating Notch signaling may constitute a useful therapeutic strategy for atherosclerosis. Key words: atherosclerosis, endothelium, signaling pathways, Notch, NF-kB, transcriptional regulation Overall design: RNA was isolated from the aortic arches of three ApoE-/-;RBPJflox/flox and three ApoE-/-; RBPJflox/flox;Cdh5-CreERTmice
Publication Title
Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and atherosclerosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The hypothesis that the oleanolic acid of olive oil might influence hepatic gene expression in an apoE was tested in mice.
Publication Title
Dietary oleanolic acid mediates circadian clock gene expression in liver independently of diet and animal model but requires apolipoprotein A1.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Multiple myeloma (MM) cells were treated with the BET inhibitor CPI203 alone and in combination with lenalidomide plus dexamethasone in vitro and in vivo (mouse xenograft).
Publication Title
The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in <i>in vitro</i> and <i>in vivo</i> models of multiple myeloma by blockade of Ikaros and MYC signaling.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
C33-A is a Homo sapiens cervix carcinoma cell line. In this experiment we determine the level of gene expression under exponentially growing conditions.
Publication Title
The chromatin remodeller CHD8 is required for E2F-dependent transcription activation of S-phase genes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 863 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Identifying the Mechanism of Action (MoA) of drugs is critical for the development of new drugs, understanding their side effects, and drug repositioning. However, identifying drug MoA has been challenging and has been traditionally attempted only though large experimental setups with little success. While advances in computational power offers the opportunity to achieve this in-silico, methods to exploit existing computational resources are still in their infancy. To overcome this, we developed a novel method to identify Drug Mechanism of Action using Network Dysregulation (DeMAND).
Publication Title
Elucidating Compound Mechanism of Action by Network Perturbation Analysis.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 105 Downloadable Samples
- Illumina HiScanSQ
Description
Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in immunomodulation in different murine models in which these cells participate. The fate of the CD4 T cells activated in the presence of the immunosuppressor or its long-term effects on these cells are however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished antibody production against specific and unrelated antigens. Transcriptionally, the salivary protein provokes a sharp acute effect that includes known activation factors, such as Il2, Cd44, or Il2ra, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with the immunomodulatory protein does not result in B cell anergy or the generation of myeloid suppressor cells. However, the immunomodulatory protein induces the increased expression of the ectoenzyme, CD73, in regulatory T cells. Our results suggest that the specific regulation of CD73, a known modulator of adenosine levels, by Salp15 results in long-term cross-antigenic immunomodulatory effects. Overall design: Genome-wide changes in gene Expression in mouse CD4 T cells activated with anti-CD3/CD28 in the presence of 25 ug/mL of the tick salivary protein, Salp15 or its inactive control (Salp15deltaP11) were generated by RNAseq.
Publication Title
The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation.
Publication Title
Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
DNA methylation changes in neuroblastoma, a clinically-heterogeneous pediatric tumor, have been described essentially in promoter regions. We analyzed the DNA methylome of neuroblastoma using high-density microarrays and observed differential methylation not only in promoters but also in intragenic and intergenic regions at both CpG and non-CpG sites. These epigenetic changes showed a non-random distribution relative functional chromatin domains, and targeted development and cancer-related genes, relevant for neuroblastoma pathogenesis. CCND1, a gene overexpressed in neuroblastoma, showed hypomethylation of gene-body and upstream regulatory regions. Furthermore, tumors with diverse clinical-risk showed clear differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation was present in clinically-favorable tumors and affected genes such as ALK, where non-CpG methylation correlated with low gene expression. Finally, we identified CpG and non-CpG methylation signatures which correlated with patients age at time-points relevant for neuroblastoma clinical behavior, and targeted genes related to neural development and neural crest regulatory network
Publication Title
DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples