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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- Homo sapiens
- 39 Downloadable Samples
- Illumina HiSeq 2500
Description
Microglia play important roles in developmental and homeostatic brain function, and influence the establishment and progression of many neurological disorders. Here, we demonstrate that renewable human iPSCs can be efficiently differentiated to microglial-like cells (iMGL) to study neurological diseases, such as Alzheimer''s disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo and whole transcriptome analysis demonstrates that they are highly similar to adult and fetal human microglia. Functional assessment of iMGLs reveal that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. We also show novel use of iMGLs to examine the effects of fibrillar Aß and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Taken together, these findings demonstrate that iMGLs can be used in high-throughput studies of microglial function, providing important new insight into human neurological disease. Overall design: Human cells were collected and analyzed for gene expression using RNA-seq.
Publication Title
iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
Sample Metadata Fields
Specimen part, Subject
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- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Carbon monoxide (CO) is an endogenous messenger that suppresses inflammation, modulates apoptosis and promotes vascular remodeling. Here, microarrays were employed to globally characterize the CO (250 ppm) suppression of early (1 h) LPS-induced inflammation in human monocytic THP-1 cells. CO suppressed 79 of 101 immediate-early genes induced by LPS; 19% (15/79) were transcription factors and most others were cytokines, chemokines and immune response genes. The prototypic effects of CO on transcription and protein production occurred early but decreased rapidly. CO activated p38 MAPK, ERK1/2 and Akt and caused an early and transitory delay in LPS-induced JNK activation. However, selective inhibitors of these kinases failed to block CO suppression of LPS-induced IL-1beta, an inflammation marker. Of CO-suppressed genes, 81% (64/79) were found to have promoters with putative NF-kappaB binding sites. CO was subsequently shown to block LPS-induced phosphorylation and degradation of IkappaBalpha in human monocytes, thereby inhibiting NF-kappaB signal transduction. CO broadly suppresses the initial inflammatory response of human monocytes to LPS by reshaping proximal events in TLR4 signal transduction such as stress kinase responses and early NF-kappaB activation. These rapid, but transient effects of CO may have therapeutic applications in acute pulmonary and vascular injury.
Publication Title
Carbon monoxide blocks lipopolysaccharide-induced gene expression by interfering with proximal TLR4 to NF-kappaB signal transduction in human monocytes.
Sample Metadata Fields
Specimen part, Treatment
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- Homo sapiens
- 60 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Peripheral whole blood transcriptome profiles of pregnant women enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation.
Publication Title
The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
Sample Metadata Fields
Sex, Specimen part, Treatment, Race
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Tacrolimus and Sirolimus are commonly used to maintain immunosuppression in kidney transplantation. However, their effects on immune cells and allograft molecular profiles have not been elucidated.
Publication Title
Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus.
Sample Metadata Fields
Specimen part, Treatment
View Samples