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SRP056125
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Context dependent molecular cues shape the formation of the cerebral vascular network and the function of the blood-brain barrier (BBB). The Wnt/ß-catenin pathway is orchestrating CNS vascular development, but downstream mediators have not been characterized. Here we generated an endothelial cell-specific R26-Axin1 overexpression (AOE) mouse model to inhibit Wnt/ß-catenin signaling. In AOE mice we discovered that blockade of Wnt/ß-catenin pathway leads to premature regression and remodeling without compromising BBB integrity. Importantly, by comparing transcriptomes of endothelial cells from wildtype and AOE mice, we identified ADAMTSL2 as a novel Wnt/ß-catenin-induced, secreted factor, important for stabilizing the BBB during development. Zebrafish loss-of-function and gain-of-function models, further demonstrated that ADAMTSL2 is crucial for normal vascular development and could rescue vascular phenotypes in AOE zebrafish brains. In conclusion, the studies presented here reveal a hitherto unrecognized role of ADAMTSL2 as an endothelial cell-specific mediator of Wnt/ß-catenin signaling during CNS vascular development and BBB-formation. Overall design: Examination of expression changes in mouse brain endothelial cells when overexpressing Axin1
Publication Title
Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of β-Catenin Signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genes regulated by the transcription factor HNF4a2
Publication Title
HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We integrated three transplant rejection microarray studies examining gene expression in samples from pediatric renal, adult renal, and adult heart transplants. We performed one study ourselves and retrieved two others from the NCBI Gene Expression Omnibus (GEO)(GSE4470 and GSE1563). We identified 45 genes that were upregulated in common in acute rejection. Half were involved in one immune-related pathway. Among ten proteins we tested by serum ELISA, three successfully distinguished acute rejection from stable transplants. These were CXCL9, PECAM1, and CD44, with areas under the receiver operating characteristic curves of 0.844, 0.802, and 0.738, respectively. Immunohistochemistry showed that the PECAM1 protein was increased in acute rejection in renal, liver and heart transplants versus normal tissues. Our results show that integrating publicly-available gene expression data sets is a fast, powerful, and cost-effective way to identify serum-detectable diagnostic biomarkers.
Publication Title
Integrative urinary peptidomics in renal transplantation identifies biomarkers for acute rejection.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
The animal piRNA pathway is a small RNA silencing system that acts in gonads and protects the genome against the deleterious influence of transposons. A major bottleneck in the field is the lack of comprehensive knowledge of the factors and molecular processes that constitute this pathway. We conducted an RNAi screen in Drosophila and identified ~50 genes that strongly impact the ovarian somatic piRNA pathway. Many identified genes fall into functional categories that indicate essential roles for mitochondrial metabolism, RNA export, the nuclear pore, transcription elongation and chromatin regulation in the pathway. Follow-up studies on two factors demonstrate the identification of components acting at distinct hierarchical levels of the pathway. Finally, we define CG2183/Gasz as a novel primary piRNA biogenesis factor in somatic and germline cells. Based on the similarities between insect and vertebrate piRNA pathways our results have far-reaching implications for the understanding of this conserved genome defense system. Overall design: Steady-state RNA levels in wild-type ovarian somatic cells (OSC) and RNAi knock-downs of the piRNA pathway components.
Publication Title
The genetic makeup of the Drosophila piRNA pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background
Publication Title
A systems biology approach reveals common metastatic pathways in osteosarcoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Large cell lymphomas of the gastrointestinal tract are currently regarded as diffuse large B-cell lymphomas despite a more favourable clinical outcome and a lower aggressiveness compared to other nodal and extranodal DLBCL. We compared gene expression profiles of 28 gastrointestinal marginal zone B-cell lymphomas and variants with several other B-cell lymphoma entities such as Burkitts lymphoma, nodal DLBCL, follicular lymphoma, mantle cell lymphoma, primary mediastinal B-cell lymphoma and normal B-cell populations. Based on a subset of NF-kappaB target genes, partitioning and hierarchical cluster algorithms were used which led to comparable results. The different B-cell subsets, the Burkitts lymphoma, and the small cell lymphomas formed distinct groups, respectively. The DLBCL were subdivided into one group containing only DLBCL samples, one subset clustered together with the PMBL samples, and another one together with the blastic variants of MZBL. These results implicate that extranodal blastic MZBL represent a distinct subgroup of DLBCL.
Publication Title
Comparative gene-expression profiling of the large cell variant of gastrointestinal marginal-zone B-cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
To investigate the function of CITED1 in melanoma, its expression was transiently down regulated using CITED1-targeting siRNA. The HT144 melanoma cell line was chosen as it had a relatively high level of detectable CITED1 mRNA and protein expression.
Publication Title
Loss of CITED1, an MITF regulator, drives a phenotype switch in vitro and can predict clinical outcome in primary melanoma tumours.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
4 replicates were prepared from A2058 melanoma cells [transfected with 10ng of empty vector (pcDNA3.1+)] and treated with 5ng/ml TGF1 or vehicle control for 24hrs
Publication Title
Loss of CITED1, an MITF regulator, drives a phenotype switch in vitro and can predict clinical outcome in primary melanoma tumours.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 117 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide DNA methylation analysis of lung carcinoma reveals one neuroendocrine and four adenocarcinoma epitypes associated with patient outcome.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 117 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis. Experimental Design Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 12 normal lung tissues and 124 tumors including 83 adenocarcinomas, 23 squamous cell carcinomas (SqCC), one adenosquamous cancer, five large cell carcinomas, nine large cell neuroendocrine carcinomas (LCNEC), and three small cell carcinomas (SCLC). Complimentary gene expression analyses was performed on 117 of the 124 tumors using Illumina HT12 V4 arrays (reported here).
Publication Title
Genome-wide DNA methylation analysis of lung carcinoma reveals one neuroendocrine and four adenocarcinoma epitypes associated with patient outcome.
Sample Metadata Fields
No sample metadata fields
View Samples