Filters
Technology
Platform
SRP068326
Mus musculus
12 Downloadable Samples
Illumina Genome Analyzer
Description
Our data represents the first analysis of histone methyltransferase Ezh2 regulated transcriptomes in mouse CD8 T cells. Overall design: Naïve and in vitro TCR stimulated CD8 T cell mRNA profiles of Pmel-1 wild type (WT) and Ezh2-/- mice were generated by deep sequencing, in triplicate, using Illumina.
Publication Title
Ezh2 phosphorylation state determines its capacity to maintain CD8<sup>+</sup> T memory precursors for antitumor immunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
BJAB cells over expressing KSHV PAN RNA
Publication Title
Regulation of viral and cellular gene expression by Kaposi's sarcoma-associated herpesvirus polyadenylated nuclear RNA.
Sample Metadata Fields
No sample metadata fields
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
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
Neuropathic pain is a complex chronic condition, characterized by a wide range of sensory, cognitive, and affective symptoms. Indeed, a large percentage of neuropathic pain patients are also afflicted with depression and anxiety disorders -- a pattern that is reliably replicated in animal models. Mounting evidence from clinical and preclinical studies indicates that chronic pain corresponds with adaptations in several brain networks involved in mood, motivation, and reward. Chronic stress is also a major determinant for depression. However, whether chronic pain and chronic stress affect similar mechanisms, and whether chronic pain can affect gene expression patterns known to be involved in depression, remains poorly understood. We employed the spared nerve injury model (SNI) of neuropathic pain in adult C57BL\6 mice and performed next-generation RNA-sequencing in order to monitor changes in gene expression in three brain regions known to be implicated in the pathophysiology of depression and in the modulation of pain: the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the periaqueductal grey (PAG). We observed mostly unique transcriptome profiles across the three brain regions but found common intracellular signal transduction pathways and biological functions were affected. A large amount of genes showing SNI-induced altered expression have been implicated in depression, anxiety, or chronic pain. In addition, we identified genes that are similarly regulated in a murine model of depression: chronic unpredictable stress. Our study provides the first unbiased characterization of neuropathic pain-induced long-term gene expression changes in three distinct brain regions, and presents evidence that neuropathic pain affects the expression of several genes that are also regulated by chronic stress. Overall design: RNA-seq samples were generated from 3 brain regions (nucleus accumbens, medial prefrontal cortex, and periaqueductal grey) of adult male mice, 2.5 months after sham or spared nerve injury to the sciatic nerve.
Publication Title
Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina HiSeq 2000
Description
Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPR). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrate that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects. Using biochemical assays and next-generation RNA sequencing, we identified a key role of RGSz1 in the periaqueductal gray (PAG) in morphine tolerance. Chronic morphine administration promotes RGSz1 activity in the PAG, which in turn modulates transcription mediated by the Wnt/ß-catenin signaling pathway to promote analgesic tolerance to morphine. Conversely, the suppression of RGSz1 function stabilizes Axin2-Gaz complexes near the membrane and promotes ß-catenin activation, thereby delaying the development of analgesic tolerance. These data show that the regulation of RGS complexes, particularly those involving RGSz1-Gaz, represents a promising target for optimizing the analgesic actions of opioids without increasing the risk of dependence or addiction. Overall design: Understanding the impact of morphine tolerance and the influence of RGSz1 on gene expression in the PAG
Publication Title
Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
The striatal protein Regulator of G protein signaling-2 (RGS9-2) plays a key modulatory role in opioid, monoamine and other GPCR responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood reward and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action. By controlling the activation of effector molecules by G protein a and bg subunits, RGS9-2 affects several protein interactions, phosphoprotein levels, and the function of the epigenetic modifier histone deacetylase 5 (HDAC5), that are important for TCA responsiveness. Furthermore, information from RNA-seq analysis reveals that RGS9-2 in the NAc affects the expression of many genes known to be involved in nociception, analgesia and antidepressant drug actions. Our findings provide novel information on NAc-specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain states. Overall design: The RNAseq study was designed in order to reveal the impact of RGS9-2 on gene regulation in the Nucleus Accumbens under neuropathic pain and antidepressant treatment conditions. A total of 18 samples was used, coprising 6 different groups , and each group consisted of three different biological replicates.
Publication Title
RGS9-2--controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the newly identified methylcytosine oxidase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We show that chronic social defeat stress, an ethologically validated mouse model of depression, decreased Tet1 expression in nucleus accumbens (NAc), a key brain reward region, in stress susceptible mice only. Surprisingly, selective knockout of Tet1 in NAc neurons of adult mice produced antidepressant-like effects in several behavioral assays. To identify Tet1 targets that mediate these actions, we performed RNAseq on NAc after Tet1 knockout and found that immune-related genes are the most highly regulated. Interestingly, many of these genes are also upregulated in NAc of resilient mice after chronic social defeat stress. Together, these findings link Tet1 to stress responses and identify novel targets for future antidepressant drug discovery efforts. Overall design: mRNA was collected from TET1 loxp/loxp mouse nucleus accumbens 4 weeks after AAV-Cre injection with AAV-GFP as control. RNAseq was then performed.
Publication Title
Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on the brain, and recent work has demonstrated the involvement of chromatin modifications in these alterations. However, all such studies to date have been restricted by their reliance on microarray technologies which have intrinsic limitations. Here, we used advanced sequencing methods, RNA-seq and ChIP-seq, to obtain an unprecedented view of cocaine-induced changes in gene expression and associated adaptations in numerous modes of chromatin regulation in the nucleus accumbens, a key brain reward region. We identify unique combinations of chromatin changes, or signatures, that accompany cocaine’s regulation of gene expression, including the dramatic involvement of pre-mRNA alternative splicing in cocaine action. Together, this delineation of the cocaine-induced epigenome in the nucleus accumbens reveals several novel modes of drug regulation, thereby providing new insight into the biological basis of cocaine addiction. More broadly, the combinatorial chromatin and transcriptional approaches that we describe serve as an important resource for the field, as they can be applied to other systems to reveal novel transcriptional and epigenetic mechanisms of neuronal regulation. Overall design: Total RNA was isolated from mouse nucleus accumbens 24 hr after 7 day daily cocaine or saline control ip injection for mRNA sequencing by following illumina RNA seq kit protocol. Another batch of acute cocaine RNA-seq was performed using the same parameters except the treatment group was given 6 days of saline injection followed by 1 day of cocaine injection. The acute cocaine batch serves as control experiments.
Publication Title
Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.
Sample Metadata Fields
No sample metadata fields
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- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
NMuMG is an epithelial cell line that can be induced into EMT by TGF- treatment or MET by TGF- withdrawl. During EMT, several marker genes were downregulated/upregulated, which is consistent with its mesenchymal phenotype.
Publication Title
Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression of integrin β4.
Sample Metadata Fields
Cell line, Treatment
View Samples