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GSE21901
Homo sapiens, Rattus norvegicus
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MicroRNAs (miRNAs) regulate many basic aspects of cell biology including neuronal plasticity, but little is known of their roles in drug addiction. Extended access to cocaine can trigger the emergence of compulsive drug-seeking behaviors, but molecular mechanisms regulating this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with extended access to cocaine. Striatal overexpression of miR-212 decreases, whereas its inhibition increases cocaine intake in rats with extended but not restricted drug access, suggesting that miR-212 serves as a protective factor against the development of compulsive drug seeking. The transcription factor CREB (cAMP response element-binding protein) is considered a core regulator of cocaine reward. We show that miR-212 controls responsiveness to cocaine by dramatically amplifying striatal CREB signaling. This action occurs through miR-212-enhanced Raf-1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (Transducer of Regulated CREB; also known as CRTC). Our findings suggest that striatal miR-212 signaling plays a key role in vulnerability to addiction, and that noncoding RNAs such as the miRNAs may serve as novel targets for the development of anti-addiction therapeutics.
Publication Title
Striatal microRNA controls cocaine intake through CREB signalling.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The adipocyte-derived hormone leptin maintains energy balance by acting on hypothalamic leptin receptors (Leprs) that trigger the signal transducer and activator of transcription 3 (Stat3). Although disruption of Lepr-Stat3 signaling promotes obesity in mice, other features of Lepr function, such as fertility, seem normal, pointing to the involvement of additional regulators. Here we show that the cyclic AMP responsive elementbinding protein-1 (Creb1)-regulated transcription coactivator-1 (Crtc1) is required for energy balance and reproductionCrtc1-/- mice are hyperphagic, obese and infertile. Hypothalamic Crtc1 was phosphorylated and inactive in leptin-deficient ob/ob mice; leptin administration increased amounts of dephosphorylated nuclear Crtc1. Dephosphorylated Crtc1 stimulated expression of the Cartpt and Kiss1 genes, which encode hypothalamic neuropeptides that mediate leptins effects on satiety and fertility. Crtc1 overexpression in hypothalamic cells increased Cartpt and Kiss1 gene expression, whereas Crtc1 depletion decreased it. Indeed, leptin enhanced Crtc1 activity over the Cartpt and Kiss1 promoters in cells overexpressing Lepr and these effects were disrupted by expression of a dominant-negative Creb1 polypeptide. As leptin administration increased recruitment of hypothalamic Crtc1 to Cartpt and Kiss1 promoters, our results indicate that the Creb1-Crtc1 pathway mediates the central effects of hormones and nutrients on energy balance and fertility.
Publication Title
The Creb1 coactivator Crtc1 is required for energy balance and fertility.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
This experiment analyzes the set of RNAs copurifying with the protein TNIP2 (amino acids 196-346) Overall design: HEK293 cells were transfected with constructs expressing either Halo tag (controls) or Halo-TNIP2 196-346. Total RNA was purified from an aliquot of the whole cell extract (Input samples). Halo-tagged proteins were purified from the remainder of the whole cell extract, and RNA subsequently purified from the Halo purified samples (Pulldown samples).
Publication Title
TNIP2 is a Hub Protein in the NF-κB Network with Both Protein and RNA Mediated Interactions.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 27 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The CREB family of transcription factors stimulates cellular gene expression following phosphorylation at a conserved serine (Ser133 in CREB1) in response to cAMP and other extracellular signals. In order to characterize CREB target genes in various tissues, we give a cAMP agonist, forskolin (FSK), to cell lines or primary cultures and monitor the gene expression. To eliminate CREB-independent effects of FSK on cellular gene expression, we employed a dominant negative form of CREB called A-CREB, which dimerizes selectively with and blocks the DNA binding activity of CREB but not other bZIP family members. Therefore, genes that are induced by cAMP and the induction was blocked by A-CREB treatment likely represents CREB target genes.
Publication Title
Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray analysis to study the expression differences between controls and hESCs expressing RB7LP for 3 days, and controls and hESCs expressing T121 for 3 days. RB7LP is the large pocket fragment of the retinoblastoma protein (RB) fused to GFP,
Publication Title
The RB family is required for the self-renewal and survival of human embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 44 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as collateral damage to other cellular components and therefore are not expected to provoke identical responses by the cell.
Publication Title
High atomic weight, high-energy radiation (HZE) induces transcriptional responses shared with conventional stresses in addition to a core "DSB" response specific to clastogenic treatments.
Sample Metadata Fields
Age, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Studies of gene expression profiles using the whole genome wide microarray analysis in SUM149PT cells (ER-, p53mut) and SUM190PT cells (ER-, p53mut) when treated with 5 or 7.5 M CG-1521 alone and in combination with 10 nM 17-Estradiol. Comparisons between each treatment group provides evidence for the dysregulation of genes associated with the spindle assembly checkpoint.
Publication Title
Histone deacetylase inhibitors modulate miRNA and mRNA expression, block metaphase, and induce apoptosis in inflammatory breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The second messenger cAMP acts via protein kinase A (PKA) to induce apoptosis by mechanisms that are poorly understood. Here, we assessed a role for mitochondria and analyzed gene expression in cAMP/PKA-promoted apoptosis by comparing wild-type (WT) S49 lymphoma cells and the S49 variant, D- (cAMP-deathless), which lacks cAMP-promoted apoptosis but has wild-type levels of PKA activity and cAMP-promoted G1 growth arrest. Treatment of WT, but not D-, S49 cells with 8-CPT-cAMP for 24 h induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and Smac and increase in caspase-3 activity. Gene expression analysis (using Affymetrix 430 2.0 Arrays) revealed that WT and D- cells incubated with 8-CPT-cAMP have similar, but non-identical, extents of cAMP-regulated gene expression at 2h (~800 transcripts) and 6h (~1000 transcripts) (|Fold|>2, P<0.06); by contrast, at 24h ~2500 and ~1100 transcripts were changed in WT and D- cells, respectively. Using an approach that combined regression analysis, clustering and functional annotation to identify transcripts that showed differential expression between WT and D- cells, we found differences in cAMP-mediated regulation of mRNAs involved in transcriptional repression, apoptosis, the cell cycle, RNA splicing, Golgi and lysosomes. The 2 cell lines differed in CREB phosphorylation and expression of the transcriptional inhibitor Icer and in cAMP-regulated expression of genes in the Inhibitor of apoptosis (IAP) and Bcl families. The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid cells occurs via mitochondrial-mediated events and imply that such apoptosis involves gene networks in multiple biochemical pathways.
Publication Title
Gene expression signatures of cAMP/protein kinase A (PKA)-promoted, mitochondrial-dependent apoptosis. Comparative analysis of wild-type and cAMP-deathless S49 lymphoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
SKBR3 cells expressing NDRG1 shRNA1 or vector control were harvested by trypsinization and total RNA was extracted. Silencing NDRG1 reduces cell proliferation rates, causing lipid metabolism dysfunction including increased fatty acid incorporation into neutral lipids and lipid droplets.
Publication Title
NDRG1 regulates neutral lipid metabolism in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
G protein coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active Gs-coupled GPCR, under the control of the 2.3 kb-Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone which were accompanied by an increase in OB lineage cells, especially immature OBs, indicated by an expansion of cells expressing Osterix and Runx2 in the whole femur. In this study, we further evaluated how Gs signaling in OBs affects intramembranous bone formation by examining calvariae of one-and nine-week-old Col1(2.3)/Rs1 mice. Rs1 calvariae displayed a dramatic increase in total volume and trabecular bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space in Rs1 expressing mice while Osteocalcin was expressed predominantly in cells along bone surfaces. These findings resembled that previously seen in Rs1 femoral bones, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb-Col I promoter could influence early OB commitment, differentiation, and/or proliferation. However, it is still unclear how G protein signaling in mature OBs leads to the observed alterations in bone mass. In this study, we investigated the cellular basis of the skeletal changes by assessing the effect of Rs1 expression in vivo on the transcriptome of mature OBs. We identified the complete set of Gs-GPCRs and other GPCRs that are expressed on OBs which may contribute to the observed skeletal phenotype. Candidate paracrine mediators of the effect of Gs signaling in OBs were determined. Genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. Our results identify novel candidate mediators of the anabolic response to the skeleton to Gs signaling in mature OBs.
Publication Title
Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive Gs-G protein signaling in osteoblasts.
Sample Metadata Fields
Specimen part
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