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GSE76644
Macaca mulatta
26 Downloadable Samples
Rhesus Gene 1.0 ST Array (rhegene10st)
Description
Handedness and language are two well-studied examples of asymmetrical brain function in humans. Approximately 90% of humans exhibit a right-hand preference, and the vast majority shows left-hemisphere dominance for language function. Although genetic models of human handedness and language have been proposed, the actual gene expression differences between cerebral hemispheres in humans remain to be fully defined. In the present study, gene expression profiles were examined in both hemispheres of three cortical regions involved in handedness and language in humans and their homologues in rhesus macaques: ventrolateral prefrontal cortex, posterior superior temporal cortex (STC), and primary motor cortex. Although the overall pattern of gene expression was very similar between hemispheres in both humans and macaques, weighted gene correlation network analysis revealed gene co-expression modules associated with hemisphere, which are different among the three cortical regions examined. Notably, a receptor-enriched gene module in STC was particularly associated with hemisphere and showed different expression levels between hemispheres only in humans.
Publication Title
Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase C (PKC) mouse model of DCM. Transgenic mice expressing constitutively active PKC in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKC mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKC mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKC mice suggests that CTGF inhibition may benefit patients with DCM.
Publication Title
Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA microenvironment promote chemotherapy delivery and improve anti-neoplastic responses in murine models of PDA. Here, we employed the FG-3019 monoclonal antibody directed against the pleiotropic matricellular signaling molecule connective tissue growth factor (CTGF/CCN2). FG-3019 treatment increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. Microarray expression profiling revealed the down-regulation by FG-3019 of several anti-apoptotic transcripts, including the master regulator Xiap, down-regulation of which has been shown to sensitize PDA to gemcitabine. Decreases in XIAP protein by FG-3019 in the presence and absence of gemcitabine were confirmed by immunoblot, while increases in XIAP protein were seen in PDA cell lines treated with recombinant CTGF. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models and, by extension, PDA patients.
Publication Title
CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina HiSeq 2000
Description
Pancreatic Ductal Adenocarcinoma (PDA) develops predominantly through pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) precursor lesions. Pancreatic acinar cells are reprogrammed to a “ductal like” state during PanIN-PDA formation. Here, we demonstrate a parallel mechanism operative in mature duct cells where they undergo “ductal retrogression” to form IPMN-PDA. Brg1, a catalytic subunit of the SWI/SNF complexes, plays a critical antagonistic role in IPMN-PDA development. In mature duct cells Brg1 inhibits the dedifferentiation that precedes neoplastic transformation, thus attenuating tumor initiation. In contrast, Brg1 promotes tumorigenesis in full-blown PDA by supporting a mesenchymal-like transcriptional landscape. We have exploited this duality of Brg1 functions to develop a novel therapeutic approach using an epigenetic drug JQ1. In summary, this study demonstrates the context-dependent roles of Brg1 and points to potential therapeutic treatment options based on epigenetic regulation in PDA. Overall design: Duct cells were isolated from mice of 3 different genotypes and duct cells from 3 mice of each genotype were sequenced. For the put back experiments, control retrovirus and that expressing Brg1 were transdcued in Brg1 null IPMN mouse cell line.
Publication Title
Brg1 promotes both tumor-suppressive and oncogenic activities at distinct stages of pancreatic cancer formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparison of mRNA expression from FACS isolated Gli1 expressing stromal cells from mice given SAG21k versus vehicle
Publication Title
Control of inflammation by stromal Hedgehog pathway activation restrains colitis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparative analysis of mRNA from colons of mice that were given colitis though use of 5% dextran sulfate in the drinking water (Days 0-5)
Publication Title
Control of inflammation by stromal Hedgehog pathway activation restrains colitis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission
Publication Title
Increased expression of neutrophil-related genes in patients with early sepsis-induced ARDS.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene silencing via heterochromatin formation plays a major role in cell differentiation and maintenance of homeostasis. Here, we report the identification and characterization of a novel heterochromatinization factor in vertebrates, Bromo Adjacent Homology Domain-containing protein 1 (BAHD1). BAHD1 interacts with HP1, MBD1, HDAC5 and with several transcription factors. Through electron and immunofluorescence microscopy studies, we show that BAHD1 overexpression directs HP1 to specific nuclear sites and promotes formation of large heterochromatic domains, which lack acetyl histone H3 and are enriched in H3 trimethylated at lysine 27. Furthermore, ectopically expressed BAHD1 colocalizes with the heterochromatic X inactive chromosome. As highlighted by whole genome microarray analysis of BAHD1 knock down cells, BAHD1 represses several proliferation and survival genes and in particular, the insulin-like growth factor II gene (IGF2). BAHD1 specifically binds the CpG-rich P3 promoter of IGF2. This region contains DNA binding sequences for the transcription factor SP1, with which BAHD1 co-immunoprecipitates. Collectively, these findings provide evidence that BAHD1 acts as a silencer by recruiting proteins that coordinate heterochromatin assembly at specific sites in the genome.
Publication Title
Human BAHD1 promotes heterochromatic gene silencing.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To study the molecular mediators of naturally rewarding effects of palatable food we used a model of palatable snacking (Ulrich-Lai et al., 2007) in which rats are given chronic, brief access to a limited amount of sucrose solution (30%). Single housed, male Long-Evans rats (250g) (n=12 per group) from Harlan Labs (Indianapolis, IN) received normal rat chow (Harlan Teklad) and water ad libitum for the duration of the experiment. After a one-week period of acclimation, rats were randomly assigned to drink treatment groups of either 30% sucrose solution or water. Rats received a 14-day regimen of twice daily (9:30 and 15:30) brief (maximum of 30 minutes) limited (up to 4 mL) access of their assigned drink solution. Drink solutions were delivered via a graduated sipper placed onto the cage top in addition to the existing water bottle and sippers were immediately removed when the animal had consumed 4mL or after the 30-minute access period, whichever occurred first. Drink intake, food intake, and body weight were monitored throughout the experiment to verify that the rats learned to drink sucrose, that they adjusted chow intake for calories consumed from sucrose (~10%), and that there was no effect on body weight gain as is normally seen with this model (Ulrich-Lai et al., 2007). Drink treatment terminated on day 14 and at 8:00 on the morning of day 15, the rats were sacrificed by rapid decapitation. BLA tissue was dissected, RNA extracted, and gene expression changes between water and sucrose groups were accessed by microarray.
Publication Title
Pleasurable behaviors reduce stress via brain reward pathways.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Most human cancers present hyperactivated sumoylation, and cancer cell lines are usually highly sensitive to the lack of it, supporting potential application of sumoylation chemical inhibitors in cancer therapy. Here, we explored the impact of hyposumoylation (Ubc9 haploinsufficiency) on cancer development in mice using Apc loss-driven intestinal tumorigenesis model.
Publication Title
An unanticipated tumor-suppressive role of the SUMO pathway in the intestine unveiled by Ubc9 haploinsufficiency.
Sample Metadata Fields
Specimen part
View Samples