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SRP058647
Homo sapiens
8 Downloadable Samples
IlluminaHiSeq2000
Description
Neuroblastoma cell lines can differentiate upon retinoic acid (RA) treatment, a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen we identify the transcriptional coactivator Mastermind-like 3 (MAML3) as a gene whose ectopic expression confers resistance to RA. We find that MAML3 expression leads to loss of activation of a subset of RA target genes, which hampers RA-induced differentiation. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the retinoic acid receptor, suggesting a role for MAML3 in the regulation of these genes. In addition, MAML3 has RA independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. Our results indicate an important role for MAML3 in differentiation and proliferation of neuroblastomas. Overall design: RNA-seq of SK-N-SH control and MAML3 overexpressing (SD3.23) cells, either untreated (UT) or treated with 1 µM RA (RA).
Publication Title
Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We investigated the nutritional effects on gene expression in sperm cells of F0 boars from a three generation Large White pig feeding experiment. A group of experimental (E) F0 boars were fed a standard diet supplemented with high amounts of methylating micronutrients whereas a control (C) group of F0 boars received a standard diet. These differentially fed F0 boars sired F1 boars which then sired 60 F2 pigs which were investigated in a previous study. The aim of this study was to investigate if the nutrition affects gene expression in sperm cells of differentially fed boars and thus carry information in the form of RNA molecules to the next generation. Four RNA samples from sperm cells of these differentially fed boars were analyzed by RNA-Seq methodology. We found no differential RNA expression in sperm cells of the two groups based on the adjusted P-value > 0.05. Nevertheless, we performed a pathway analysis with 105 genes that differed in gene expression on the level of nominal P-value < 0.05 between the two diet groups. We found a significant number of these differentially expressed genes were enriched for the pathway maps of bacterial infections in cystic fibrosis (CF) airways, glycolysis and gluconeogenesis p.3 and cell cycle_Initiation of mitosis. The GO processes including a significant portion of differentially expressed genes were viral transcription and viral genome expression, viral infectious cycle, cellular protein localization, cellular macromolecule localization, nuclear-transcribed mRNA catabolic process and nonsense-mediated decay. In summary, the results of the pathway analysis are also inconclusive and it is concluded that RNA expression in sperm cells is not significantly affected by extensive supplementation of methylating micronutrients. Consequently, RNA molecules could not be established as epigenetic marks in this feeding experiment. Overall design: Gene expression in sperm cells from differentially fed F0 boars was measured. F0 boars received either a standard diet or a standard diet supplemented with methylating micronutrients. These boars were used to study transgenerational epigenetic inheritance in a three generation pig pedigree. Therefore it was of interest if the diet affects gene expression in sperm cells which could then be transmitted to next generations.
Publication Title
In search of epigenetic marks in testes and sperm cells of differentially fed boars.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Human myoblast cell line 54-1 is transfected with either a srambled control siRNA or siRNA against UPF1. Two days after transfection, cell were induced to differentiate by changing grow meida to differentiation media. 2 days after induction of differentiation, cells are collected for extraction of RNA. Overall design: Human myoblast cell line 54-1 is transfected with either a srambled control siRNA or siRNA against UPF1. Two days after transfection, cell were induced to differentiate by changing grow meida to differentiation media. 2 days after induction of differentiation, cells are collected for extraction of RNA.
Publication Title
The RNA Surveillance Factor UPF1 Represses Myogenesis via Its E3 Ubiquitin Ligase Activity.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2500
Description
Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. Overall design: Two TSC+/- cell lines and two TSC-/- cell lines were independently generated from wild-type human embryonic stem cells by genome editting with zinc finger nucleases. Two cell lines were handled in the same way but without any known human gene editted and they are used as negative controls. Two independent biological replicates of each of the six cell lines are profiled with ribosome profiling technique.
Publication Title
Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the transcriptome-wide gene expression changes underlying chemical conversion of human fibroblasts into induced Schwann Cells over a time period of 39 days. We compared then the expression profiles of these induced Schwann Cells to primary Schwann cells.
Publication Title
Chemical conversion of human fibroblasts into functional Schwann cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 1500
Description
Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of the double-homeodomain transcription factor DUX4 in skeletal muscle cells. Many different cell culture models have been developed to study the pathophysiology of FSHD, frequently based on endogenous expression of DUX4 in FSHD cells or by mis-expression of DUX4 in control human muscle cells. Although results generated using each model are generally consistent, differences have also been reported, making it unclear which model(s) faithfully recapitulate DUX4 and FSHD biology. In this study, we systematically compared RNA-seq data generated from three different models of FSHD—lentiviral-based DUX4 expression in myoblasts, doxycycline-inducible DUX4 in myoblasts, and differentiated human FSHD myocytes expressing endogenous DUX4—and show that the DUX4-associated gene expression signatures of each dataset are highly correlated (Pearson's correlation coefficient, r ~ 0.75-0.85). The few robust differences were attributable to different states of cell differentiation and other differences in experimental design. Our study describes a model system for inducible DUX4 expression that enables reproducible and synchronized experiments and validates the fidelity and FSHD relevance of multiple distinct models of DUX4 expression. Overall design: We performed a systematic comparison of DUX4-regulated changes in the transcriptome in our inducible codon-altered DUX4 expression system (iDUX4), the endogenous DUX4 expression system (enDUX4), and cells transduced with lentivirus constitutively expressing DUX4 (vDUX4). The specific datasets used in this comparison are as follows: iDUX4 represents a new dataset generated from the MB135 immortalized human myoblasts with the doxycycline inducible codon-altered DUX4 (iDUX4), performed in biological triplicate fourteen hours after DUX4 induction in growth media, with uninduced cells as a control; enDUX4 represents the published dataset of differentiated FSHD myocytes that do or do not express endogenous DUX4, as determined using a DUX4-responsive fluorescent reporter and flow sorting (9); vDUX4 represents a published dataset wherein two different myoblast cell lines (MB135 and 54-1) were transduced with a lentiviral construct that drives constitutive DUX4 expression via the PGK promoter and maintained in growth media for 24 hours (MB135) or 36 hours (54-1) prior to harvesting RNA.
Publication Title
Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
Cell fate specification of neural stem/progenitor cells (NSCs) is an intricate developmental process that determines neural cell identity. While transcriptional mechanisms undoubtedly affect this process, translational mechanisms are much less understood. Here we show that deficiency of the chromatin remodeler Chromodomain Helicase DNA binding protein 5 (Chd5) causes transcriptional de-repression of multiple ribosomal subunit genes, increases protein synthesis, and expands the activated stem cell pool leading to perturbation of NSC fate. Compromised H3K27me3 in Chd5 deficient NSCs during early cell fate specification underlies the generation of excessive astrocytes at the expense of neurons at later stages of differentiation. Chd5 expression rescues these cell fate defects while simultaneously reestablishing H3K27me3, and inhibition of the H3K27me3-specific demethylase Utx restores appropriate cell fate specification in NSCs lacking Chd5. These findings define a Chd5-Utx-H3K27me3 axis pivotal in ribosome biogenesis and translation during neurogenesis, consistent with compromised CHD5 being implicated in glioma. Overall design: mRNA profiles of primary neural/stem progenitor cells (NSCs) of wild type (+/+) and Chd5-/- mice were generated, in duplicate, using Illumina NextSeq 500.
Publication Title
Chromatin-mediated translational control is essential for neural cell fate specification.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2500
Description
Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons. Overall design: RNA-seq of FACS sorted PV+ and SST+ cortical interneuronals at P8 of wt and conditional Rbfox1 Kos
Publication Title
Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Arabidopsis thaliana transcription factor LATERAL ORGAN BOUNDARIES (LOB) is expressed in the boundary between the shoot apical meristem and initiating lateral organs. To identify genes regulated by LOB activity, we used an inducible 35S:LOB-GR line. This analysis identified genes that are differentially expressed in response to ectopic LOB activity.
Publication Title
Arabidopsis lateral organ boundaries negatively regulates brassinosteroid accumulation to limit growth in organ boundaries.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
We have discovered rifampicin as a glycation inhibitor, which increases life span in C elegans. In order to understand the mechanism of rifampicin action, microarray analysis was performed to study the changes in gene expression brought about by the drug.
Publication Title
Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.
Sample Metadata Fields
Specimen part
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