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GSE65623
Mus musculus
12 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Nrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in lung cancer.
Publication Title
Dimethyl fumarate and the oleanane triterpenoids, CDDO-imidazolide and CDDO-methyl ester, both activate the Nrf2 pathway but have opposite effects in the A/J model of lung carcinogenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The purpose of this study was to search for microgravity-sensitive genes, specifically for apoptotic genes influenced by the microgravity environment and other genes related to immune response.
Publication Title
Gene expression alterations in activated human T-cells induced by modeled microgravity.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 14 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Karrikins promote seed germination in Arabidopsis thaliana. Completion of germination (protrusion of the radicle) is not observed until ~72 h in dormant wildtype seed under these conditions. We used microarrays to examine karrikin-induced transcriptional changes after 24 h of imbibition. Transcriptional changes may indicate events leading to karrikin-induced germination or karrikin-specific markers.
Publication Title
Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The below table includes a smaller list of data that was analyzed by dChip and filtered by pvalue such that a file with about 4600 genes was obtained, which allowed for ease of use from 40,000 genes.
Publication Title
Identification of mechanosensitive genes in osteoblasts by comparative microarray studies using the rotating wall vessel and the random positioning machine.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
2,3,7,8-TCDD (TCDD) is a reproductive toxicant and endocrine disruptor in nearly all vertebrates, yet the mechanisms by which TCDD induces these reproductive alterations have not been fully characterized. Fish are among the most sensitive vertebrates to the toxic effects of TCDD, and even subtle physiologic changes induced by TCDD can impair reproduction. Previously, we have shown that chronic, sub-lethal exposure to TCDD decreased reproductive capacity, reduced serum estradiol and vitellogenin concentrations, and altered follicular development. Here we investigate the transcriptional changes in zebrafish ovary as they relate to observed attenuated estradiol concentrations and ovarian development. We used quantitative RT-PCR to assess TCDDs effects on the expression of several candidate genes important in the regulation of follicular development and steroidogenesis. Additionally, global changes in gene expression in the ovary caused by TCDD exposure were identified using Affymetrix Gene Chip Analysis. Our data suggest that TCDD may inhibit follicle maturation via attenuated gonadotropin responsiveness and/or depressed estradiol biosynthesis. Additionally, genes involved in glucose and lipid metabolism, regulation of transcription, and immune function were dysregulated by at least 2-fold suggesting that TCDD alters various integrated networks of signaling pathways. Approximately 89% of dysregulated transcripts contain putative AHR response elements (AHRE) within 5kb upstream of the predicted transcriptional start site suggesting ovarian toxicity is AHRE driven. Furthermore, approximately 49% of dysregulated transcripts contain putative estrogen response elements (ERE) suggesting that dysregulation of estrogen-responsive genes may also contribute to TCDD-induced attenuated follicular development. Patterns in gene expression were correlated with putative EREs and AHREs, and suggest that impacts on the regulation of transcription may play a large role in TCDDs ovarian toxicity. Taken together, these data illustrate the complexity of TCDDs ovarian toxicity.
Publication Title
Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina Genome Analyzer II
Description
The miR-16 family, which targets genes important for the G1-S transition, is a known modulator of the cell cycle, and members of this family are often deleted or down-regulated in many types of cancers. Here we report the reciprocal relationship - that of the cell cycle controlling the miR-16 family. Levels of this family increase rapidly as cells are arrested in G0. Conversely, as cells are released from G0 arrest, levels of the miR-16 family rapidly decrease. Such rapid changes are made possible by the unusual instabilities of several family members. The repression mediated by the miR-16 family is sensitive to these cell cycle changes, which suggests that the rapid up-regulation of the miR-16 family reinforces cell cycle arrest in G0. Upon cell cycle re-entry, the rapid decay of several members allows levels of the family to decrease, alleviating repression of target genes and allowing proper resumption of the cell cycle. Overall design: Small RNAs were profiled by high-throughput sequencing either during synchronous release after serum starvation or during cell-cycle arrest by contact inhibition.
Publication Title
MicroRNA destabilization enables dynamic regulation of the miR-16 family in response to cell-cycle changes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Illumina HiSeq 2500
Description
Translation and mRNA decay are intimately connected processes, and translational inhibition often precedes and stimulates transcript degradation. Here, we have focused on methods that allow determination of mRNA stability on a transcriptome-wide scale. We describe experimental and computational methods for the two most commonly used approaches (transcriptional inhibition and metabolic labeling), and we discuss associated caveats. Overall design: Metabolic labeling time courses (1, 2, 4, 8, 12, 24 hr) using 4SU were performed in HEK293.
Publication Title
Determining mRNA half-lives on a transcriptome-wide scale.
Sample Metadata Fields
Treatment, Subject
View Samples- Danio rerio
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Olfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein ß? subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron. Overall design: Total 6 samples were analyzed-3 controls & 3 samples
Publication Title
Normalization of RNA-seq data using factor analysis of control genes or samples.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Abstract. The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation, however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were co-cultured with vascular cells. Co-culture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Post-transfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression which was directly related to the transfer. Infusion of wild-type platelets into a TLR2 deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, it was also observed that external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis.
Publication Title
Platelets and platelet-like particles mediate intercellular RNA transfer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 384 Downloadable Samples
- Illumina HiSeq 2500
Description
Midbrain dopamine neurons project to numerous targets throughout the brain to modulate various behaviors and brain states. Within this small population of neurons exists significant heterogeneity based on physiology, circuitry, and disease susceptibility. Recent studies have shown that dopamine neurons can be subdivided based on gene expression; however, the extent to which genetic markers represent functionally relevant dopaminergic subpopulations has not been fully explored. Here we performed single-cell RNA-sequencing of mouse dopamine neurons and validated studies showing that Neurod6 and Grp are selective markers for dopaminergic subpopulations. Using a combination of multiplex fluorescent in situ hybridization, retrograde labeling, and electrophysiology in mice of both sexes, we defined the anatomy, projection targets, physiological properties, and disease vulnerability of dopamine neurons based on Grp and/or Neurod6 expression. We found that the combinatorial expression of Grp and Neurod6 defines dopaminergic subpopulations with unique features. Grp/Neurod6 dopamine neurons reside in the ventromedial VTA, send projections to the medial shell of the nucleus accumbens, and have noncanonical physiological properties. Grp/Neurod6- DA neurons are found in the VTA as well as in the ventromedial portion of the SNc, where they project selectively to the dorsomedial striatum. Grp-/Neurod6 DA neurons represent a smaller VTA subpopulation, which is preferentially spared in a 6-OHDA model of Parkinson's disease. Together, our work provides detailed characterization of Neurod6 and Grp expression in the midbrain and generates new insights into how these markers define functionally relevant dopaminergic subpopulations with distinct projection patterns, physiology, and disease vulnerability. Overall design: We collected a total of 384 neurons from 8 different p26-p34 DAT-Cre::Ai9 mice (6 male 2 female) to isolate DA neurons. RNA was captured from each samples neurons on separate fluidigm chips then all samples were pooled before sequencing.
Publication Title
Combinatorial Expression of <i>Grp</i> and <i>Neurod6</i> Defines Dopamine Neuron Populations with Distinct Projection Patterns and Disease Vulnerability.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples