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SRP078061
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
Total mRNA seq was perfomed on widtype and Ret null mouse embryonic gut at 2 stages of devlopment- E11.5 and E12.5 Overall design: Total RNA from 3 replicates each of wildtype and Ret null emryonic gut was converted to cDNA and run on HiSeq 2000 (75 bp paired end)
Publication Title
Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 77 Downloadable Samples
- Illumina HiSeq 2000
Description
Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is required for maintenance of MCC and can transform normal cells. To gain insight into cellular perturbations induced by MCPyV ST, we performed transcriptome analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST dynamically alters the cellular transcriptome with increased levels of glycolytic genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1). Extracellular flux analysis revealed increased lactate export reflecting elevated aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90 cells. Both NF-?B and MYC have been shown to regulate MCT1 expression. While MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased following knockdown of the NF-?B subunit RelA, supporting a synergistic activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more effective than MYC or MYCN in increasing extracellular acidification in MCC cells. Our results demonstrate the effects of MCPyV ST on the cellular transcriptome and reveal that transformation is dependent, at least in part, on elevated aerobic glycolysis. Overall design: Expression of MCPyV ST or GFP was induced in IMR90 fibroblasts, and triplicate RNA samples were extracted and sequenced every 8 hours for a total of 96 hours
Publication Title
Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic Perturbations Required for Transformation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
To determine if EP400 knockdown would affect Max target genes in Merkel cell carcinoma cell line MKL-1, we performed RNA-seq analyses of MKL-1 cells inducibly expressing EP400 shRNA and compared to ChIP-seq data using BETA analyses. Overall design: EP400 was inducibly reduced with shRNA in MKL-1 cells to analyze gene regulation.
Publication Title
Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
An RNA-seq dataset obtained from neural fold-stage chicken (Gallus gallus, strain Special Black) embryos that were exposed to a pharmacologically-relevant alcohol concentration (52 mM for 90 min) or isotonic saline. The cranial headfolds were isolated 6 hours following the initial alcohol exposure. Following RNA isolation, cDNA synthesis, and quality assurance (20), paired-end reads (75 bp) were generated on an Illumina Genome Analyzer IIx (University of Wisconsin Biotechnology Center). Overall design: Paired end runs with 2 replicate ethanol exposed samples (pool of 23 individual neural folds) and 2 saline control samples (pool of 23 individual neural folds).
Publication Title
Exon level machine learning analyses elucidate novel candidate miRNA targets in an avian model of fetal alcohol spectrum disorder.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains that contribute to the viral life cycle, including the DNA binding and helicase domains. In addition, the LT the C-terminal region is required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells and identified interacting cellular proteins and performed expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes.
Publication Title
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Coinhibitory receptor blockade is a promising strategy to boost immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for improved understanding of checkpoint blockade, but the T cell-intrinsic signaling pathways and gene expression profiles engaged during treatment are not well defined, particularly for combination approaches. We utilized a murine model of CD8+ T cell tolerance to address these issues.
Publication Title
Checkpoint blockade immunotherapy relies on T-bet but not Eomes to induce effector function in tumor-infiltrating CD8+ T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Background: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Publication Title
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to impact gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that can prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor a binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine tune the expression of target genes. Overall design: The effects of Enhancer interference (Enhancer-i) and control guide RNA treatment on the transcriptome before and after estrogen treatment, with 2 replicates per condition.
Publication Title
Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program.
Publication Title
MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NK cells develop in the bone marrow and complete their maturation in peripheral organs, but the molecular events controlling maturation are incompletely understood. Utilizing an NK cell-specific miR-15/16 deficient genetic model (15aKO), we identified a critical role for miR-15/16 family microRNAs in the normal maturation of NK cells in vivo, with a specific reduction in mature CD11b+CD27- NK cells in multiple tissues. The mechanism responsible was a block in differentiation, since accelerated NK cell death was not evident, and earlier intermediates of NK cell maturation were expanded. Further, we identified Myb as a direct target of miR-15/16 in NK cells, with Myb expression increased in immature 15aKO NK cells. Following adoptive transfer, immature 15aKO NK cells exhibited defective maturation, which was rescued by ectopic miR-15/16 expression or Myb knockdown. Moreover, Myb overexpression resulted in defective NK cell maturation. Thus, miR-15/16 regulation of Myb controls the normal NK cell maturation program.
Publication Title
MicroRNA-15/16 Antagonizes Myb To Control NK Cell Maturation.
Sample Metadata Fields
Specimen part
View Samples