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SRP102546
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- Danio rerio
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
We report the gene expression comparison of zebrafish melanocytes and melanomas. These comparisons were used for integrative genomic studies that identified the BMP factor GDF6 as a new oncogene that is specifically expressed in melanomas. Overall design: Examination of gene expression in two different cell types
Publication Title
Ligand-activated BMP signaling inhibits cell differentiation and death to promote melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2500
Description
Gene expression analysis of primary mouse prostate organoid culture with overexpression of FOXA1 Overall design: Examination by genotypes and days elapsed prepared in 3 replicates
Publication Title
FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.
Sample Metadata Fields
Subject, Time
View Samples- Danio rerio
- 8 Downloadable Samples
- NextSeq 500
Description
Selenium, one of a class of selenocysteine-containing proteins (selenoproteins), is an essential micronutrient known for its cancer prevention properties. Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LCMS/ MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels. Overall design: 4 WT zebrafish samples and 4 SepH mutant samples
Publication Title
Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
F4/80+ macrophages treated with TGFb2 are potently tolerogenic. Our understanding of the molecular mechanisms mediating the development of these tolerogenic properties is incomplete.
Publication Title
FcγRI is required for TGFβ2-treated macrophage-induced tolerance.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 165 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
To investigate the cellular responses induced by air pollution exposures, we performed genome-wide gene expression microarray analysis using whole blood RNA sampled at three time-points across the work weeks of 63 non-smoking employees in the trucking industry. Our objective was to identify the genes and gene networks differentially activated in response to micro-environmental measures of occupational exposure to three pollutants: PM2.5 (particulate matter 2.5 microns in diameter) and elemental carbon (EC) and organic carbon (OC).
Publication Title
Gene expression network analyses in response to air pollution exposures in the trucking industry.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The complex response of murine macrophages to infection with Streptococcus pyogenes was investigated at the level of gene expression using a high-density oligomer microarray. More than 400 genes were identified as being differentially regulated. Many of the up-regulated genes encoded molecules were involved in immune response and inflammation, transcription, signalling, apoptosis, cell cycle, electron transport and cell adhesion. Of particular interest was the up-regulation of proinflammatory cytokines, typical of the classically activated macrophages (M1 phenotype) such as TNF-?, IL-1 and IL-6, and also the up-regulation of anti-inflammatory mediators such as IL-1ra and IL-10 associated with macrophage alternative activation (M2 phenotype). Furthermore, the gene encoding inducible nitric oxide synthase (iNOS), an enzyme typically implicated in classical activation was not induced in infected macrophages. Instead, the gene encoding arginase, a competitor for the iNOS substrate arginine and involved in the alternative activation pathway was up-regulated in S. pyogenes-infected cells. Thus, the microarray-based gene expression analysis demonstrated that S. pyogenes induced an atypical activation program in macrophages with some but not all features of classically or alternatively activation phenotypes. The microarray data also suggested that the bactericidal activity of macrophages against S. pyogenes is mediated by phagocyte oxydase since p47phox was up-regulated in infected cells. Indeed, the in vivo and in vitro killing of S. pyogenes was markedly diminished in the absence of functional phagocyte (p47phox-/-) but not in the absence of iNOS (iNOS-/-). Understanding how macrophages respond to S. pyogenes at the molecular level may facilitate the development of new therapeutic paradigms.
Publication Title
Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
The potential safety issues related to the acquisition of common genomic aberrations in hPSC cultures are well-recognized, but these risks have not been evaluated for sporadic mutations. Here, we explore whether a sporadic mutation that spontaneously arose in a hESC culture consisting of a single-copy deletion of chr17p13.1 would confer a survival advantage to the mutant cells. Compared to wild-type cells with two normal copies of the chr17p13.1 region, the mutant cells displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of pluripotent cells after two weeks of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by the deleted region, in wild-type cells mimicked the chr17p13.1 deletion phenotype. RNA sequencing analysis showed differential expression of genes in pathways related to proliferation and differentiation. Thus, phenotypic implications of sporadic mutations must be taken into consideration before using the hPSC for clinical applications. Overall design: Triplicate cDNA libraries of two mutant WA09 lines with a single-copy deletion of chr17p13.1, and two wild-type WA09 lines, for a total of 12 libraries were sequenced using Illumina HiSeq 2500. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.
Publication Title
Spontaneous Single-Copy Loss of TP53 in Human Embryonic Stem Cells Markedly Increases Cell Proliferation and Survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 313 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Whole human fetal lung transcriptome profiles from estimated gestational ages 54 to 137 days post conception. Maternal cigarette smoking status is indicated by cotinine levels measured in the corresponding placenta.
Publication Title
Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples