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GSE85570
Homo sapiens
437 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate -H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual -H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed 2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of -H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer
Publication Title
Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 28 Downloadable Samples
Illumina HiSeq 2500
Description
Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving), but the transcriptional mechanisms that contribute to this incubation are unknown. Here we used RNA-sequencing to analyze transcriptional profiles associated with incubation of Meth craving in central amygdala (CeA) and orbitofrontal cortex (OFC), two brain areas previously implicated in relapse to drug seeking. We trained rats to self-administer either saline (control condition) or Meth (10 days; 9 h/day, 0.1 mg/kg/infusion). Next, we collected brain tissue from CeA and OFC on withdrawal day 2 (when Meth seeking is low and non-incubated) and on day 35 (when Meth seeking is high and incubated), for subsequent RNA-sequencing. In CeA, we identified 10-fold more differentially expressed genes (DEGs) on withdrawal day 35 than day 2. These genes were enriched for several biological processes, including protein ubiquitination and histone methylation. In OFC, we identified many fewer expression changes than in CeA. Interestingly, there were more DEGs on withdrawal day 2 than on day 35. Several genes in OFC showed opposing expression changes on withdrawal day 2 (increase) when compared to withdrawal day 35 (decrease), which was further validated by qPCR. Our analyses highlight the CeA as a key region of transcriptional regulation associated with incubation of Meth seeking. In contrast, transcriptional regulation in OFC may contributes to Meth seeking during early withdrawal. Overall, these findings provide a unique resource of gene expression data for future studies examining transcriptional mechanisms in CeA that mediate Meth seeking after prolonged withdrawal. Overall design: Exp. 1 Genome-wide transcriptional profiling of CeA during incubation of Meth craving We performed intravenous surgeries on two groups of rats (total n=26) and trained them to self-administer either saline (n=12) or Meth (n=14) as described above in 2 independent runs. We performed live decapitation on withdrawal days 2 and 35, and collected CeA tissue for mRNA preparation. We used the extracted mRNA for library preparation and RNA-sequencing. We pooled tissue from two rats as one biological replicate. The number of biological replicates in each group was: Day 2: Saline=3, Meth=4; Day 35: Saline=3, Meth=3. Exp. 2 Genome-wide transcriptional profiling of OFC during incubation of Meth craving As above, two groups of rats (total n=32) were trained to self-administer saline (n=16) or Meth (n=16) in 2 independent runs. We performed live decapitation on withdrawal days 2 and 35, and collected OFC tissue for mRNA preparation. We used the extracted mRNA either for library preparation and RNA-sequencing or for cDNA synthesis and qPCR. We pooled tissue from two rats as one biological replicate. The number of biological replicates in each group was: Day 2: Saline=4, Meth=4; Day 35: Saline=4, Meth=4.
Publication Title
Genome-wide transcriptional profiling of central amygdala and orbitofrontal cortex during incubation of methamphetamine craving.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
Saccharomyces cerevisiae cannot metabolize cellobiose in nature. Here, S. cerevisiae was engineered to achieve cellobiose utilization by introducing both a cellodextrin transporter gene (cdt-1) and an intracellular ß-glucosidase gene (gh1-1) from Neurospora crassa. We sequenced mRNA from anaerobic exponential cultures of engineered S. cerevisiae grown on cellobiose or glucose as a single carbon source in biological triplicate. Differences in gene expression between cellobiose and glucose metabolism revealed by RNA deep sequencing indicated that cellobiose metabolism induced mitochondrial activation and reduced amino acid biosynthesis under fermentation conditions. Overall design: mRNA levels in cellobiose-grown and glucose-grown cells of engineered cellobiose-utilizing Saccharomyces cerevisiae were examined by deep sequencing, in triplicate, using Illumina Genome Analyzer-II. We sequenced 3 samples from cellobiose-grown cells and 3 samples from glucose-grown cells and identified differential expressions in the cellobiose versus glucose fermentations by using mRNA levels of glucose-grown cells as a reference.
Publication Title
Leveraging transcription factors to speed cellobiose fermentation by Saccharomyces cerevisiae.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cels, that work together to maintain steady-state respiration. Due to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systemically identify these subsets in human airways, by developing a schema of isolating large numbers of cells by whole lung bronchoalveolar lavage. Six subsets of phagocytic antigen presenting cells were consistently observed, which varied in their ability to internalize bacterial particles. Subsets could be further separated by their inherent capacities to upregulate CD83, CD86, and CCR7. Whole genome transcriptional profiling revealed a clade of true dendritic cells distinct from a macrophage/monocyte clade. Each clade, and each member of both clades, could be discerned by specific genes of increased expression, which would serve as markers for future studies in healthy and diseased states.
Publication Title
Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.
Sample Metadata Fields
Sex, Age
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- NextSeq 500
Description
The goal of this study was to determine how decreased mitochondrial citrate export influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila sea mutants, which exhibiti decreased mitochondrial citrate transport activity, and a genetically-matched control strain during mid-L3 development. Overall design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.
Publication Title
A <i>Drosophila</i> model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
2-methoxyestradiol (2ME2) induces mammary gland differentiation through amphiregulin-EGFR mediated signaling: molecular distinctions from the mammary gland of pregnant mice.High levels of 2ME2 are observed in the late stages of pregnancy. We investigated the role of 2ME2 on normal mammary gland development. Large scale gene expression assays were performed using Affymetrix GeneChips in pursuit of detailed molecular basis. (1) Mammary glands of wild type FVB mice administered 75 or 150 mg/kg of 2ME2 (2) Mammary glands of normal FVB/Nj mice (i) at day 16 of pregnancy, (ii) day 2 of lactation (iii) day 30 of post-lactation, and (3) mammary epithelial SCp2 cells after 6, 24 and 48 hours of 10 micromol 2ME2 treatment were examined. In vivo studies revealed that 2ME2 treatment up regulates the expression of amphiregulin. The clue to the role of 2ME2 in differentiation comes from studies in vitro which detected down regulation of inhibitor of differentiation (Id-1) gene and consequent up regulation of amphiregulin. The differentiation of E2 negative SCp2 cells by 2ME2 indicate estradiol independent mechanism. For details, please see our paper in Endocrinology 2006.
Publication Title
2-methoxyestradiol induces mammary gland differentiation through amphiregulin-epithelial growth factor receptor-mediated signaling: molecular distinctions from the mammary gland of pregnant mice.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 140 Downloadable Samples
- Illumina HiSeq 2000
Description
Depression is a complex and heterogeneous disorder and a leading contributor to the global burden of of disease. Most previous research has focused on individual brain regions and individual genes that contribute to depression. However, emerging evidence in both humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here we use a bioinformatics approach intersecting differential expression analysis with weighted gene co-expression network analysis to identify transcriptional networks that regulate susceptibility to depressive-like symptoms in mice. We performed RNA-sequencing on multiple brain regions from control animals and those either susceptible or resilient to chronic social defeat stress (CSDS) at multiple time points after defeat. We bioinformatically identified several transcriptional networks that regulate depression susceptibility, and in vivo manipulations of these networks confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our findings reveal novel transcriptional networks that control stress susceptibility and offer fundamentally new leads for antidepressant drug discovery. Overall design: RNA-seq samples were generated from 4 brain regions (nucleus accumbens (NAC), prefrontal cortex (PFC), amygdala (AMY) and ventral hippocampus (VHIP) ) at 3 time-points (48h, 28d, 28d +1h stress) after chronic social defeat stress in control, susceptible and resilient mice. Additionally, RNA-seq samples were generated from virally infected VHIP tissue (HSV-GFP or HSV-Dkkl1) after an accelerated social defeat to assess the effect of Dkkl1 over-expression.
Publication Title
Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina Genome Analyzer
Description
The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex (PRC2)-induced H3-K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin (Nnat) to decrease intracellular calcium (Ca2+) level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Functional complementation experiments with Nnat-3’UTR mutant, which is refractory to suppression by miR-708, rescued cell migration and metastasis defects. In breast cancer patients, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer. Overall design: Sequencing miRNAs from Human breast cancer cells: MCF10A, MCF7, MDA-MB-231, MDA-MB-LM2
Publication Title
Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Cancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
Publication Title
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Sample Metadata Fields
Specimen part
View Samples