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SRP115944
Rattus norvegicus
12 Downloadable Samples
Illumina HiSeq 3000
Description
Reduced eukaryotic Initiation Factor 2 (eIF2)a phosphorylation (p-eIF2a) enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2a has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2a in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1). The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP)-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2a in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ?FosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2a and the gateway drug properties of psychoactive cannabinoids. Overall design: RNAseq from PC12 cell line with a 6 hour DMSO or WIN treatment.
Publication Title
Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Publication Title
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT).
Publication Title
Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Mice overexpressing galectin-8 (gal-8 Tg), a secreted mammalian lectin, exhibit enhanced bone turnover and reduced bone mass, similar to cases of post-menopausal osteoporosis. Gal-8 knockout (KO) mice have increased bone mass accrual at young age, but exhibit accelerated bone loss during adulthood. These phenotypes can be attributed to gal-8-mediated increase in RANKL expression that promotes osteoclastogenesis, combined with direct inhibition of osteoblasts differentiation, evident by reduced BMP signaling, SMAD phosphorylation, and reduced expression of osteoblasts differentiation markers OSX, OCN, RUNX2, DMP-1 and ALP. Gal-8 mRNA positively correlates with the mRNA levels of osteoclastogenic markers RANKL, TRAP and CTSK in human femurs. Collectively, these findings identify gal-8 as a new physiological player in the regulation of bone mass.
Publication Title
Ablation of the mammalian lectin galectin-8 induces bone defects in mice.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify the CAR-, PXR- and PPAR-specific genome-wide expression changes, hepatocyte cultures from six individual donors were treated with the prototypical ligands for
Publication Title
Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression was measured from the dentate gyrus and entorhinal cortex harvested from human postmortem samples.
Publication Title
Molecular mechanism for age-related memory loss: the histone-binding protein RbAp48.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We asked whether combining Notch and VEGF blockade would enhance suppression of tumor angiogenesis and growth, using the NGP neuroblastoma model. NGP tumors were engineered to express a Notch1 decoy construct (N1D), which restricts Notch signaling, and then treated with either the anti-VEGF antibody bevacizumab or vehicle. Combining Notch and VEGF blockade led to blood vessel regression, increasing endothelial cell apoptosis and disrupting pericyte coverage of endothelial cells. Combined Notch and VEGF blockade did not affect tumor weight, but did additively reduce tumor viability. Our results indicate that Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis, and show that concurrent blockade disrupts primary tumor vasculature and viability further than inhibition of either pathway alone.
Publication Title
Notch and VEGF pathways play distinct but complementary roles in tumor angiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We examined the biological effects of a potent second-generation proteasome inhibitor, ixazomib, in T-cell lymphoma and Hodgkin lymphoma cell lines and human xenograft models. Ixazomib resulted in time- and dose-dependent cytotoxicity and apoptosis in all cell lines (IC50s <75nM). In vivo studies via SCID tumor xenografts showed significant inhibition of tumor growth (P<0.001) with significantly improved survival (P<0.001) in Jurkat and L540 models with ixazomib-treated mice versus controls. Through global transcriptome and network analyses, ixazomib-treated Jurkat and L540 cells showed significant overlap in biological functions involved in regulation of cell cycle, chromatin modification, and DNA repair processes with a lack of conservation observed in a relatively ixazomib-resistant cell line, L428. Moreover, the predicted activation and inhibition status of tumor suppressors and oncogenes strongly favored ixazomib inhibition of tumor progression. Most notably, ixazomib down-regulated protein levels of MYC and its target genes. Additionally, chromatin immunoprecipitation showed that histone H3 acetylation affected MYC levels and cell death response to ixazomib. Furthermore, inhibition of MYC with JQ1 resulted in synergistic cell death in L428, which was confirmed utilizing MYC knockout. Collectively, ixazomib down-regulated MYC and downstream substrates in TCL and HL, while resistance appeared mediated through MYC- and CHK1-dependent mechanisms.
Publication Title
Proteasomal Inhibition by Ixazomib Induces CHK1 and MYC-Dependent Cell Death in T-cell and Hodgkin Lymphoma.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The objective of this study was to reprogram peripheral blood-derived late-endothelial progenitor cells (EPCs) to a pluripotent state under feeder-free and defined culture conditions. Late-EPCs were retrovirally-transduced with OCT4, SOX2, KLF4, c-MYC, and iPSC colonies were derived in feeder-free and defined media conditions. EPC-iPSCs expressed pluripotent markers, were capable of differentiating to cells from all three germ-layers, and retained a normal karyotype. Transcriptome analyses demonstrated that EPC-iPSCs exhibit a global gene expression profile similar to human embryonic stem cells (hESCs). We have generated iPSCs from late-EPCs under feeder-free conditions. Thus, peripheral blood-derived late-outgrowth EPCs represent an alternative cell source for generating iPSCs.
Publication Title
Feeder-independent derivation of induced-pluripotent stem cells from peripheral blood endothelial progenitor cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is growing evidence that transplantation of cadaveric human islets is an effective therapy for type 1 diabetes. However, gauging the suitability of islet samples for clinical use remains a challenge. We hypothesized that islet quality is reflected in the expression of specific genes. Therefore, gene expression in 59 human islet preparations was analyzed and correlated with diabetes reversal after transplantation in diabetic mice. Analysis yielded 262 differentially expressed probesets, which together predict islet quality with 83% accuracy. Pathway analysis revealed that failing islet preparations activated inflammatory pathways, while functional islets showed increased regeneration pathway gene expression. Gene expression associated with apoptosis and oxygen consumption showed little overlap with each other or with the 262 probeset classifier, indicating that the three tests are measuring different aspects of islet cell biology. A subset of 36 probesets surpassed the predictive accuracy of the entire set for reversal of diabetes, and was further reduced by logistic regression to sets of 14 and 5 without losing accuracy. These genes were further validated with an independent cohort of 16 samples. We believe this limited number of gene classifiers in combination with other tests may provide complementary verification of islet quality prior to their clinical use.
Publication Title
Gene expression signature predicts human islet integrity and transplant functionality in diabetic mice.
Sample Metadata Fields
Specimen part
View Samples