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SRP014662
Mus musculus
7 Downloadable Samples
Illumina Genome Analyzer IIx
Description
The complexity of the mature adult brain is a result of both developmental processes and experience-dependent circuit formation. One way to look at the process of brain development is to examine gene expression changes, and previous studies have used microarrays to address this in a global manner. However, the transcriptome is more complex than gene expression levels alone, as both alternative splicing and RNA editing occur to generate a more diverse set of mature transcripts. The aim of the current study was to develop a high-resolution transcriptome dataset of mouse cortical development using RNA sequencing (RNA-Seq), thus assaying exon usage and RNA editing as well as overcoming some of the inherent limitations of microarrays. We found a large number of differentially expressed genes, but also altered splicing and RNA editing between embryonic and adult cerebral cortex. Each dataset was validated both technically and biologically, and in each case tested we found our RNA-Seq observations to have high predictive validity. We propose this dataset, and the accompanying analysis, to be a helpful resource in the understanding of changes in gene expression during development. Overall design: Three young adult cerebral cortices four embryonic cerebral cortices
Publication Title
mRNA expression, splicing and editing in the embryonic and adult mouse cerebral cortex.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 705 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.
Publication Title
Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 584 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on DNA methylation, mRNA expression and microRNA (miRNA) expression in four distinct human brain regions. We show that brain tissues may be readily distinguished based on methylation status or expression profile. We find an abundance of genetic cis regulation mRNA expression and show for the first time abundant quantitative trait loci for DNA CpG methylation. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation.
Publication Title
Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
M cells are the main site of bacterial translocation in the intestine. We used the in vitro M cell model to study the effect of the commensal bacteria; Lactobacillus salivarius, Eschericha coli and Bacteroides fragilis, on M cell gene expression.
Publication Title
Differential intestinal M-cell gene expression response to gut commensals.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ulipristal acetate (UPA), also referred to as VA/CDB-2914, is a new and promising emergency contraceptive. It is a selective progesterone receptor modulator (SPRM) that has been approved in Europe and the USA for emergency contraception.
Publication Title
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Previous studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles.
Publication Title
Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- NextSeq 500
Description
The pathognomonic EWS/ETS fusion transcription factors drive Ewing sarcoma (EWS) by orchestrating an oncogenic transcription program. Therapeutic targeting of EWS/ETS has not been successful; therefore identifying mediators of the EWS/ETS function could offer new therapeutic targets. Here we describe the dependency of chromatin reader BET bromodomain proteins in EWS/ETS driven transcription and investigate the potential of BET inhibitors in treating this lethal cancer. Similar to EWS/ETS fusions, knockdown of BET proteins BRD2/3/4 severely impaired the oncogenic phenotype of EWS cells. Notably, EWS/FLI1 and EWS/ERG was found to be in a transcriptional complex consisting of BRD4. RNA-Seq analysis upon BRD4 knockdown or its pharmacologic inhibition by the BET inhibitor JQ1 revealed an attenuated EWS/ETS transcriptional signature. In contrast to other reports, JQ1 reduced proliferation, and induced apoptosis through MYC-independent mechanism without affecting EWS/ETS protein levels, which was further confirmed by depleting BET proteins using PROTAC-BET degrader (BETd). Interestingly, polycomb repressive complex 2 (PRC2) associated factor PHF19 was downregulated by JQ1/BETd or BRD4 knockdown in multiple EWS cells. ChIP-seq analysis revealed occupancy of EWS/FLI1 at a distal regulatory element of PHF19 and its subsequent knockdown resulted in downregulation of PHF19 expression. Furthermore, deletion of PHF19 by CRISPR-Cas9 system lead to a decreased tumorigenic phenotype and increased sensitivity to JQ1. Importantly, PHF19 expression was associated with worse prognosis of Ewing sarcoma patients. In vivo, JQ1 demonstrated anti-tumor efficacy in multiple mouse xenograft models of EWS. Together, these results indicate that EWS/ETS require BET epigenetic reader proteins for its transcriptional program including PHF19 expression, which can be mitigated by BET inhibitors. Moreover, this study provides a clear rationale for the clinical utility of BET inhibitors in treating Ewing sarcoma. Overall design: Gene epxression by RNAseq in the ewing sarcoma cell lines with knockdown of EWS-FLI1, BRD4 or JQ1 treament, knockout of PHF19
Publication Title
EWS/ETS-Driven Ewing Sarcoma Requires BET Bromodomain Proteins.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis. These tumors were s.c. explanted in xenograft models for subsequent treatment experiments.
Publication Title
Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine the differential expression of KRAS-variant HNSCC (head and neck squamous cell carcinoma) cell lines.
Publication Title
A 3'-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples