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SRP007579
Mus musculus
6 Downloadable Samples
Illumina Genome Analyzer
Description
Tbx20 is a transcription factor important for heart development. To assess the role of Tbx20 in the adult heart, we generated a conditional knockout for this gene, specifically in cardiomyocytes. We profiled gene expression levels using RNA-seq in both normal and knockout adult mouse hearts to identify genes and pathways regulated by Tbx20. The article describing the Tbx20 knockout mouse is under review, a reference will be added when published. Overall design: Analysis of triplicate mRNA samples of adult mouse, comparing normal and knockout
Publication Title
Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We generated mice with a transgenic BAC on a B6 background. The BAC contains Glo1, and the transgenic mice were found to overexpress Glo1.
Publication Title
Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: to identify genes aberrantly expressed upon myocardial ablation of Hif1a Methods: a floxed Hif1a allele was deleted in mouse embryonic hearts using a NXK2.5Cre line. Total RNA was extracted from E12.5 hearts (n=3 for controls and mutants) usinz Trizol and processed for RNA-seq. Reads were mapped to Mm10 reference genome using TopHat2 and Bowtie2. Transcript expression values were determined after transcript normalization with AltAnalyze Results: this analysis revealed a total of 1451 genes significantely (|Fold| > 20% and P<0.05) modulated in Hif1a cKO hearts Overall design: 6 total RNAseq runs with 3 experimental samples and 3 controls samples
Publication Title
HIF1α Represses Cell Stress Pathways to Allow Proliferation of Hypoxic Fetal Cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a death domain (Raidd) functions as a dual adaptor protein due to its bipartite nature, and is therefore thought to be a constituent of different multiprotein complexes including the PIDDosome, where it connects the cell death-related protease, Caspase-2, with the p53-induced protein with a death domain 1 (Pidd1). As such, Raidd has been implicated in DNA-damage-induced apoptosis as well as in tumor suppression, the latter based on its role as a direct activator of Caspase-2, known to delay lymphomagenesis caused by overexpression of c-Myc or loss of ATM kinase. As loss of Caspase-2 leads to an acceleration of tumor onset in the E-Myc mouse model we set out to interrogate the role of Raidd in this process in more detail. Our data obtained analyzing E-Myc/Raidd-/- mice indicate that Raidd is unable to protect from c-MYC-driven lymphomagenesis. Similarly, we failed to observe an effect of Raidd-deficiency on thymic lymphomagenesis induced by y-irradiation or fibrosarcoma development driven by 3-methylcholanthrene. The role of Caspase-2 as a tumor suppressor can therefore be uncoupled from its ability to interact and auto-activate upon binding to Raidd. Further, we provide supportive evidence that the tumor suppressive role of Caspase-2 is related to maintaining genomic integrity and allowing efficient p53-mediated signaling. Overall, our findings suggest that Raidd, although described to be the key-adapter allowing activation of the tumor suppressor Caspase-2, fails to suppress tumorigenesis in vivo.
Publication Title
The tumor-modulatory effects of Caspase-2 and Pidd1 do not require the scaffold protein Raidd.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: huex10stv2_67_020 (huex10st)
Description
Glucocorticoids (GCs) are a central component in treating childhood acute lymphoblastic leukemia (chALL). They mainly act via regulating gene transcription. However, control of mRNA translation by GC has never been assessed systematically. In our research, T- and precursor B-ALL cells were cultured with and without GC for 6 hours and subjected to translational profiling, a technique combining sucrose gradient fractionation and microarray analysis of mRNA in different fractions. Analysis of GC regulation in different pools revealed no significant differences in regulation of mRNA translation by GC, suggesting no evidence for translational regulation by GC.
Publication Title
Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Danio rerio
- 3 Downloadable Samples
- IlluminaHiSeq2000
Description
Human oncogenes involved in the development of hematological malignancies have been widely used to model experimental leukemia. Here, we used the fli1 promoter in zebrafish to target the expression of oncogenic HRAS to endothelial cells, including the hemogenic endothelium and observed the development of a myelo-erythroid proliferative disease. In larvae, the pathological phenotype is characterized by some disruption of the vascular system with prominent expansion of the caudal hematopoietic tissue, increase of expression of stem cell markers and myelo-erythroid specific genes and production of a large number of l-plastin leukocytes. In mosaic juveniles, increased number of hematopoietic blasts and arrest of myeloid maturation was found in kidney marrow. Peripheral blood showed delays of erythrocyte maturation and increased number of circulating myeloid progenitors. We found that the abnormal phenotype is associated with a down regulation of the Notch pathway as shown by the decrease of expression of Notch target genes, whereas overexpressing an activated form of Notch together with the oncogene prevents the expansion of the myelo-erythroid compartment. This study identifies the downregulation of the Notch pathway following an oncogenic event in the hemogenic endothelium as an important step in the pathogenesis of myelo-erythroid diseases and describes a number of potential effectors of this transformation. Overall design: Methods: mRNA profiles of transgenic zebrafish overexpressing the oncogene HRAS in endothelial cells (Tg(fli1ep:GAL4FF)ubs3; Tg(UAS:eGFP-HRASV12)io006); or expressing activate Notch in endothelial cells (Tg(fli1ep:GAL4FF)ubs3; tg(UAS:NICD)kca3) were generated by deep sequencing using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed using the CLC bio Assembly Cell software (version 3.2) and the Ensembl (release 63) predicted cDNAs for the Zv9 genome assembly. qRT–PCR validation was performed using TaqMan and SYBR Green assays.
Publication Title
Targeting oncogene expression to endothelial cells induces proliferation of the myelo-erythroid lineage by repressing the Notch pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 14 Downloadable Samples
- IlluminaHiSeq2000
Description
Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAFV600E. Through the use of real-time in vivo imaging we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAFV600E. Adult zebrafish expressing BRAFV600E in thyrocytes developed invasive carcinoma. We identified a gene expression signature from zebrafish thyroid cancer that is predictive of disease free survival in patients with papillary thyroid cancer. Gene expression studies nominated TWIST2 as a key effector downstream of BRAF. Using CRISPR/Cas9 to genetically inactivate a TWIST2 orthologue, we suppressed the effects of BRAFV600E and restored thyroid morphology and hormone synthesis. These data suggest that expression of TWIST2 plays a role in an early step of BRAFV600E-mediated transformation. Overall design: 3 embryo tg-TOM (tg:TdTomato), 3 embryo tg-BRAFV600E-TOM, 3 adult tg-TOM and 5 adult tg-BRAFV600E-TOM biological replicates were sequenced. Strains with tg:TdTomato express the TdTomato fluorophore under control of the zebrafish thyroglobulin promoter (tg).
Publication Title
Oncogenic BRAF disrupts thyroid morphogenesis and function via twist expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pituitary tumor-transforming gene (PTTG1) is a recently discovered oncogene implicated in the malignant progression of a number of neoplasms. It has been shown to drive both endocrine and non-endocrine malignancies, but has not yet been studied in the context of renal cell carcinoma (RCC). Clear cell RCC (ccRCC) is cytogenetically characterized by deletion of chromosome 3p, harboring the von-Hippel Lindau tumor suppressor gene, and amplification of chromosome 5q. The significance of copy number gain of chromosome 5 is not clear, but is presumed to be the location of oncogenes that influence ccRCC development or progression. The PTTG1 oncogene maps to chromosome 5q, and here we show that PTTG1 is amplified in clear cell RCC, is overexpressed in tumor tissue relative to adjacent normal kidney, and expression is associated with high grade, high stage, and poor prognosis. Furthermore, we establish a functional role for PTTG1 in ccRCC tumorigenesis and progression. PTTG1 ablation reduces both the tumorigenic ability of ccRCC cells in vitro and in vivo and the invasive ability of these cells in vitro. An analysis of genes whose transcription is regulated by PTTG1 was supportive of an association with invasive and metastatic disease. PTTG1-dependent expression of the Rho-GEF ECT2, another proto-oncogene, is observed in a number of ccRCC cell lines, and ECT2 expression correlates with PTTG1 expression, high stage, high grade, and poor prognosis ccRCC. As GEF's have been promoted as potential drug targets for targeted cancer therapeutics, the relationship between the PTTG1 and ECT2 oncogenes may be able to be exploited for the treatment of this disease.
Publication Title
Expression of the PTTG1 oncogene is associated with aggressive clear cell renal cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 261 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To select signatures of ccRCC, 265 ccRCC samples were obtained from the Van Andel Research Institute.
Publication Title
Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity.
Sample Metadata Fields
Specimen part, Subject
View Samples