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SRP159661
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
Purpose: The goals of this study are to compare transcriptome profiling (RNA-seq) in pancreatic intraepithelial neoplasm (PanIN) cells exposed to tobacco-specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and to examine the upregulated pathways. Overall design: Methods: Total RNA was isolated from PanIN cells treated with tobacco specific nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for 5 and 50 days. Samples were processed for RNA-seq using standard methods on the Illumina HiSeq 2000 platform. Sequencing was performed in two multiplexed lanes of 100-bp single-end sequencing, which resulted in 75 million mappable reads per lane. The Illumina pipeline was used for base calling and quality filtering of sequence reads. Transcript assembly and abundance estimates of transcripts in fragments per kilobase of exon per million fragments mapped (FPKM) were performed by Cufflinks. Significant differences in total gene and transcript expression, splice site, transcription start site (TSS) and promoter usage were determined using a false discovery rate (FDR)-adjusted P-value. This study provides a framework for understanding transcriptional changes when pancreas cells exposed to tobacco specific nitrosamine.
Publication Title
Tobacco Carcinogen-Induced Production of GM-CSF Activates CREB to Promote Pancreatic Cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Danio rerio
- 100 Downloadable Samples
- NextSeq 500
Description
Germ plasm, the Balbiani body and nuage are evolutionary conserved structures essential for germ cell specification and maintenance. We describe Tdrd6a as a component of these structures with two distinct molecular functions. First, Tdrd6a facilitates the accumulation of the typical antisense-bias of piRNAs, without having effects on piRNA biogenesis signatures. Second, we show that Tdrd6a is required for Balbiani body and germ plasm integrity, and associates with RNA-binding proteins and germ plasm mRNAs. On the cell-biological level, maternally contributed Tdrd6a strongly impacts germ cell formation, but is dispensable for fertility. Using single-cell RNA-sequencing we demonstrate that Tdrd6a promotes early germ cell development and regulates the stoichiometry of germ plasm mRNAs. We propose that Tdrd6a functions as a scaffold to recruit correct ratios of germ plasm transcripts and to accumulate antisense piRNA complexes in order to ensure both specification and maintenance of germ cells. Overall design: Single cell were sorted directly in Trizolfrom embryos spawned by mz tdrd6a-/- mother and wt mother carrying a kop::egfp-f-nos1-3'UTR transgene. Thereafter single cell trizol extractio was performed followed by RT, IVT and RNA-seq library prep.
Publication Title
Tdrd6a Regulates the Aggregation of Buc into Functional Subcellular Compartments that Drive Germ Cell Specification.
Sample Metadata Fields
Cell line, Subject
View Samples- Caenorhabditis elegans
- 47 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Transgenic animals were engineered to express human amyloid peptide controlled by a muscle-specific, heat-inducible promoter. At low temperatures (16C) Abeta expression is minimal, while at higher temperatures (20-25C) Abeta accummulates in large quantities and causes paralysis.
Publication Title
Identifying Aβ-specific pathogenic mechanisms using a nematode model of Alzheimer's disease.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 54 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We recently have identified one of the MAGE gene members, Mageb16 to be highly expressed in undifferentiated murine embryonic stem cells (mESCs). The role of Mageb16 for the differentiation of the pluripotent stem cells is completely unknown. Here we demonstrate that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated mESCs. A transcriptome study was performed with differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD ESCs) and scrambled control (SCR) ESCs until a period of 22 days. Mageb16 KD ESCs mainly differentiated towards mesodermal derivatives such as cardiovascular lineages. Mesoderm-oriented differentiation initiated biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were significantly enriched in the differentiated Mageb16 KD ESCs. Cardiomyogenesis in differentiated KD mESCs was stronger when compared to differentiated SCR and wild mESCs. The expression of non-coding RNA (ncRNA) Lin28a and other epigenetic regulatory genes, nucleocytoplasmic trafficking and genes participating in spermatogenesis have also declined faster in the differentiating Mageb16 KD ESCs. We conclude that Mageb16 plays a crucial role for differentiation of ESCs, specifically to the mesodermal lineages. Regulative epigenetic networks and nucleocytoplasmic modifications induced by Mageb16 may play a role for the critical role of Mageb16 for the ESCs differentiation.
Publication Title
Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
ICU acquired weakness (ICUAW) is a complication of critical illness characterized by structural and functional impairment of skeletal muscle that may persist for years after ICU discharge with many survivors developing protracted courses with few regaining functional independence. Elucidating molecular mechanisms underscoring sustained ICUAW is crucial to understanding outcomes linked to different morbidity trajectories as well as for the development of novel therapies. Quadriceps muscle biopsies and functional measures of muscle strength and mass were obtained at 7 days and 6 months post-ICU discharge from a cohort of ICUAW patients. Unsupervised co-expression network analysis of transcriptomic profiles identified discrete modules of co-expressed genes associated with the degree of muscle weakness and atrophy in early and sustained ICUAW. Modules were enriched for genes involved in skeletal muscle regeneration and extracellular matrix deposition. Collagen deposition in persistent ICUAW was confirmed by histochemical stain. Modules were further validated in an independent cohort of critically ill patients with sepsis-induced multi-organ failure and a porcine model of ICUAW, demonstrating disease-associated conservation across species and peripheral muscle type. Our findings provide a pathomolecular basis for sustained ICUAW, implicating aberrant expression of distinct skeletal muscle structural and regenerative genes in early and persistent ICUAW.
Publication Title
Transcriptomic analysis reveals abnormal muscle repair and remodeling in survivors of critical illness with sustained weakness.
Sample Metadata Fields
Sex, Age
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Comparative analysis of Endodermal-like cell lines with demonstrated ability to support myocardial differentiation
Publication Title
A comparative analysis of extra-embryonic endoderm cell lines.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Metazoan transcription is controlled through either coordinated recruitment of transcription machinery to the gene promoter, or subsequently, through regulated pausing of RNA polymerase II (Pol II) in early elongation. We report that a key difference between genes that use these distinct regulatory strategies lies in the chromatin architecture specified by their DNA sequences. Pol II pausing is prominent at highly-regulated genes whose sequences inherently disfavor nucleosome formation within the gene, but favor nucleosomal occlusion of the promoter. Pausing of polymerase maintains these genes in an active state by inhibiting the formation of repressive promoter chromatin. In contrast, promoters of housekeeping genes that lack paused Pol II are deprived of nucleosomes regardless of polymerase binding, but show higher nucleosome occupancy downstream. Our results suggest that the default chromatin state of a gene instructs its regulation, and that highly-regulated promoters have evolved to encourage competition between nucleosomes and paused Pol II for promoter occupancy.
Publication Title
Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Dengue is one of the most important arboviruses in the world, with 2.5 billion people living in areas under risk to contagious. Mosquitos from Aedes genus is the transmission vector of viral particles.
Publication Title
Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.
Sample Metadata Fields
Specimen part, Time
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate NF-kB family members. We have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways, and triggered activation of a STAT binding activity. Genetic experiments showed that the JAK kinase Hopscotch was involved in the control of the viral load in infected flies, and was required, though not sufficient, for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third evolutionary conserved innate immunity pathway operates in drosophila and counters viral infection.
Publication Title
The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila.
Sample Metadata Fields
No sample metadata fields
View Samples