Filters
Technology
Platform
SRP070657
Homo sapiens
30 Downloadable Samples
IlluminaHiSeq2500
Description
Estrogen receptor a (ERa) is an important biomarker of breast cancer severity and a common therapeutic target. Recent studies have demonstrated that in addition to its role in promoting proliferation, ERa also protects tumors against metastatic transformation. Current therapeutics antagonize ERa and interfere with both beneficial and detrimental signaling pathways stimulated by ERa. The goal of this study is to uncover the dynamics of coding and non-coding RNA (microRNA) expression in response to estrogen stimulation and identify potential therapeutic targets that more specifically inhibit ERa-stimulated growth and survival pathways without interfering with its protective features. To achieve this, we exposed MCF7 cells (an estrogen receptor positive model cell line for breast cancer) to estrogen and prepared a time course of paired mRNA and miRNA sequencing libraries at ten time points throughout the first 24 hours of the response to estrogen. From these data, we identified three primary expression trends—transient, induced, and repressed—that were each enriched for genes with distinct cellular functions. Integrative analysis of paired mRNA and microRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217—an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that over-expression of miR-503 suppresses breast cancer cell proliferation. Overall, these data indicate that miR-503 acts as a potent estrogen-induced tumor suppressor microRNA that opposes cellular proliferation and has promise as a therapeutic for breast cancer. More generally, our work provides a systems-level framework for identifying functional interactions that shape the temporal dynamics of gene expression. Overall design: Quantification of mRNAs in MCF7 cells responding to estrogen following a period of estrogen starvation. Three independent biological replicates (30 samples: 3 replicates x 10 time points) of MCF7 cells were exposed to 10nM Estradiol for 0, 1, 2, 3, 4, 5, 6, 8, 12 , or 24 hours, and total RNA was extracted from the samples. Total RNA was used to generate paired RNA and miRNA sequencing. RNA libraries were prepared using an Illumina TruSeq stranded mRNA library preparation kit.
Publication Title
An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed deep sequencing of small RNA from mouse insulinoma (MIN6) cells cultured in 25mM glucose. We then developed and implemented an in-house short-read mapping strategy to analyze isomiR diversity. Overall design: Profile of miRNA expression in MIN6 cells cultured in 25mM glucose.
Publication Title
Beta cell 5'-shifted isomiRs are candidate regulatory hubs in type 2 diabetes.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We characterized monosaccharide-dependent gene expression in the Drosophila fat body using fructose and glucose. Control and high-sugar diets were compared and RNA-seq was used to identify potential target genes. Overall design: Drosophila were reared on control (0.3 M fructose or glucose) or high sugar (1.7 M fructose or glucose) diets until the wandering third instar stage. Fat bodies were isolated and RNA was extracted to determine the effects of each sugar at different concentrations on gene expression using Illumina RNA-seq.
Publication Title
Similar effects of high-fructose and high-glucose feeding in a Drosophila model of obesity and diabetes.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 26 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We compared gene expression in the Drosophila fat body on control and high-sugar diets in order to gain insight into the role of this organ during caloric overload. Differential expression analysis revealed changes in gene expression suggestive of a role for CoA metabolism in the ability to tolerate high-sugar feeding. This led us to perform biochemical and mutant studies supporting a model where CoA is limiting in the face of caloric overload. Overall design: Wild-type Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Publication Title
CoA protects against the deleterious effects of caloric overload in Drosophila.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The lack of mouse models permitting the specific ablation of tissue-resident macrophages and monocyte-derived cells complicates understanding of their contribution to tissue integrity and to immune responses. Here we use a new model permitting diphtheria-toxin (DT)-mediated depletion of those cells and in which dendritic cells are spared. We showed that the myeloid cells of the mouse ear skin dermis are dominated by a population of melanin-laden macrophages, called melanophages, that has been missed in most previous studies. By using gene expression profiling, DT-mediated ablation and parabiosis, we determined their identity including their similarity to other skin macrophages, their origin and their dynamics. Limited information exist on the identity of the skin cells responsible for long-term tattoo persistence. Benefiting of our knowledge on melanophages, we showed that they are responsible for retaining tattoo pigment particles through a dynamic process which characterization has direct implications for improving strategies aiming at removing tattoos.
Publication Title
Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine Cytomegalovirus (MCMV) infection leads to early activation of various immune cells, including B and T lymphocytes, before the actual initiation of antigen-specific adaptive immunity. This activation is partly driven by innate cytokines, including type I interferon (IFN), which are induced early after infection. The objective of this study was to address the role of type I IFN in shaping early/innate B and T cell responses to a primary acute viral infection.
Publication Title
Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 70 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We compared four transcription factor knockdowns using transgenic RNAi expressed in the larval fat body. FOXO, Tfb1, p53, and Stat92E-dependent gene expression in the Drosophila fat body was quantified on control and high-sugar diets in order to generate expression profiles via RNA-seq. These expression data were used to build a gene regulatory network to predict novel roles for these and other genes during caloric overload. Overall design: Control and fat body-expressed transcription factor RNAi Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M or 1M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Publication Title
Seven-Up Is a Novel Regulator of Insulin Signaling.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Drosophila melanogaster
- 17 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
Chronic high sugar feeding induces obesity, hyperglycemia, and insulin resistance in flies and mammals. These phenotypes are controlled by the fat body, a liver- and adipose- like tissue in Drosophila flies. To gain insight into the mechanisms underlying the connection between diet and insulin sensitivity, we used Illumina RNA-seq to profile gene expression in fat bodies isolated from chronically high sugar fed, wandering (post-prandial) third instar wild type larvae w(L3). These data were compared to control-fed wild-type wL3 fat bodies as well as those expressing transgenic interfering RNA (i) targeting CG18362 (Mio/dChREBP) in the fat body on both diets. Overall design: Female VDRC w1118, cgGAL4, UAS-Dcr2 or UAS-ChREBPi(52606), cgGAL4, UAS-Dcr2 wandering third instar larvae were fed control (0.15M) or high (0.7M) sucrose and fat bodies isolated for RNA extraction.
Publication Title
Seven-Up Is a Novel Regulator of Insulin Signaling.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Muscle Expression of SOD1(G93A) Modulates microRNA and mRNA Transcription Pattern Associated with the Myelination Process in the Spinal Cord of Transgenic Mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We compared ecdysone receptor (EcR)-dependent gene expression in the Drosophila fat body on 0.15 M sucrose and 0.5 M sucrose high-sugar diets in order to gain insight into the role of this gene during caloric overload. Phenotypic analyses showed an increased severity of EcR RNAi phenotypes with increasing dietary sugar concentration. Because EcR is a transcription factor, we performed RNA-seq studies to identify transcriptional targets that might underlie insulin resistance downstream of EcR RNAi. Overall design: Control and fat body-expressed EcR RNAi Drosophila were reared on control (0.15 M sucrose) and high-sugar (0.5 M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.
Publication Title
Seven-Up Is a Novel Regulator of Insulin Signaling.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples