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SRP028611
Caenorhabditis elegans
10 Downloadable Samples
Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
During each life cycle germ cells preserve and pass on both genetic and epigenetic information. In C. elegans, the ALG-3/4 Argonaute (AGO) proteins and their small-RNA cofactors are expressed during male gametogenesis and promote male fertility. Here we show that the CSR-1 AGO functions with ALG-3/4 to positively regulate target genes required for spermiogenesis. Our findings suggest that ALG-3/4 functions during spermatogenesis to amplify a small-RNA signal that represents an epigenetic memory of male-specific gene expression, while CSR-1, which is abundant in mature sperm, transmits this memory to offspring. Surprisingly, in addition to small RNAs targeting male-specific genes, we show that males also harbor an extensive repertoire of CSR-1 small RNAs targeting oogenesis-specific mRNAs. Together these findings suggest that C. elegans sperm transmit not only the genome but also epigenetic binary signals in the form of Argonaute/small-RNA complexes that constitute a memory of which genes were active in preceding generations. Overall design: Examine small RNA changes in WT and alg-3/4 mutant males cultured at 20°C and 25°C, as well as determine the small RNAs enriched in a FLAG::CSR-1 IP from male worms grown at 25°C. mRNA sequencing was also performed to determine how transcripts targeted by small RNAs change in mutant background at 20°C and 25°C.
Publication Title
Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
From preliminary experiments, HSP70 deficient MEF cells display moderate thermotolerance to a severe heatshock of 45.5 degrees after a mild preshock at 43 degrees, even in the absence of hsp70 protein. We would like to determine which genes in these cells are being activated to account for this thermotolerance.
Publication Title
Microarray analysis of cellular thermotolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Ovis aries
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
To investigate the molecular bases of diet induced differences in milk composition, we collected milk from mid lactation dairy ewes and after 3 weeks of diet supplementation with extruded linseed. RNAs were isolated from milk somatic cells isolated from milk of 3 sheep and Illumina RNA sequencing was performed to analyze RNA synthesis in these cells. Overall design: Transcriptional profiling of milk somatic cells of sheep fed with normal diet and with a supplementation with extruded linseed. Sequence data were generated by deep sequencing, on three replicates, using Illumina HiSeq2000.
Publication Title
Transcript profiling in the milk of dairy ewes fed extruded linseed.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 251 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 251 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Publication Title
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Pre-LVAD and explanted ischemic and nonischemic cardiomyopathy and nonfailing hearts all normalized with RMA
Publication Title
Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma.
Publication Title
miR-146a promotes the initiation and progression of melanoma by activating Notch signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina Genome Analyzer
Description
Oncogenic mutations in BRAF and NRAS occur in 70% of melanomas. Here we identify a microRNA, miR-146a, that is highly upregulated by oncogenic BRAF and NRAS. Expression of miR-146a increases the ability of human melanoma cells to proliferate in culture and form tumors in mice, whereas knockdown of miR-146a has the opposite effects. We show these oncogenic activities are due to miR-146a targeting the NUMB mRNA, a repressor of Notch signaling. Previous studies have shown that pre-miR-146a contains a single nucleotide polymorphism (C>G rs2910164). We find that the ability of pre-miR-146a/G to activate Notch signaling and promote oncogenesis is substantially higher than that of pre-miR-146a/C. Analysis of melanoma cell lines and matched patient samples indicates that during melanoma progression pre-miR-146a/G is enriched relative to pre-miR-146a/C, resulting from a C-to-G somatic mutation in pre-miR-146a/C. Collectively, our results reveal a central role for miR-146a in the initiation and progression of melanoma. Overall design: WI-38 cells were either infected with BRAFV600E or Empty retroviral vectors and small RNA were prepared from these cells. As an additional control, WI-38 cells were serum starved and used to generate quiscent cells, which were also used to prepase small RNA. The small RNA were then used to generate small RNA library and were used on Illumina genome analyzer.
Publication Title
miR-146a promotes the initiation and progression of melanoma by activating Notch signaling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene Expression Array (primeview), Illumina HumanHT-12 V4.0 expression beadchip, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the United States Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for sequence discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed, for these and qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcriptlevel profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.
Publication Title
A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. We made induced pluripotent stem cell (iPSC) lines from HD patients and controls. Though no obvious effects of the CAG expansion on reprogramming or subsequent neural stem cell (NSC) production were seen, HD-NSCs showed CAG expansion-associated gene expression patterns and, upon differentiation, changes in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death for both medium and longer CAG repeat expansions, with some deficits greater in cells from longer repeat HD NSCs. The HD180 lines were more vulnerable than control lines to cellular stressors and BDNF withdrawal using a range of assays across consortium laboratories. This HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics.
Publication Title
Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples