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GSE77558
Homo sapiens
12 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Huntingtons disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons under defined culture conditions. Analysis of differentially expressed genes between Huntingtons disease and wild type iPSCs derived GABA MS-like neurons has been performed.
Publication Title
Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 106 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study, we have utilized microarray analysis to directly compare a subset of structurally distinct, clinically relevant SERMs in the presence and absence of estradiol, using a high replicate number (10) to ensure detection of modestly regulated genes.
Publication Title
Research resource: Transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by ErbB and other tyrosine-kinase receptors. Heregulin, a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by P-Rex1 in the context of HRG stimulation. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10, a gene encoding for metalloproteinase-10, was found to be highly sensitive both to P-Rex1 depletion as well as inhibition of Rac1 function by the GTPase Activating Protein (GAP) 2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.
Publication Title
Characterization of a P-Rex1 gene signature in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
IlluminaHiSeq2000
Description
Staphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention. Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection. Overall design: mRNA expression analysis. 16 samples are from 2 donors, 8 samples per donor, 2 time points (4hr and 16 hr), and 4 conditions (control, TSLP treated, Heat Killed MRSA treated, and TSLP+HKM treated) .
Publication Title
A TSLP-complement axis mediates neutrophil killing of methicillin-resistant <i>Staphylococcus aureus</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We report that decreased expression and activity of AhR exacerbates murine neovascular age-related macular degeneration, and increases cell migration and tube formation. The mechanism involves increased expression of pro-angiogenic mediators and altered matrix degradation. The results of our study suggest that the AhR signaling pathway may be important in multiple AMD related pathways. Overall design: Gene expression analysis in the retinal pigment epithelium (RPE)-choroid tissue from AhR knockout mice contrasted against wild-type age-matched controls.
Publication Title
Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mononuclear phagocytes play an important role in the removal of apoptotic cells by expressing cell surface receptors that recognize and remove apoptotic cells. Based on the knowledge that cigarette smoking is associated with increased lung cell turnover, we hypothesized that alveolar macrophages (AM) of normal cigarette smokers may exhibit enhanced expression of apoptotic cell removal receptor genes. AM obtained by bronchoalveolar lavage of normal non-smokers (n=11) and phenotypic normal smokers (n=13, 36 6 pack-yr) were screened for mRNA expression of all known apoptotic cell removal receptors using Affymetrix HG-U133 Plus 2.0 chips with TaqMan RT-PCR confirmation. Of the 14 known apoptotic receptors expressed, only MER Tyrosine Kinase (MERTK), a transmembrane tyrosine kinase receptor, was significantly up-regulated in smokers. MERTK expression was then assessed in AM of smokers vs nonsmokers by TaqMan RT-PCR, immunohistochemistry, Western and flow analysis. Smoker AM had up-regulation of MERTK mRNA levels (smoker vs non-smoker, 3.6-fold by microarray, p<0.003; 9.5-fold by TaqMan RT-PCR, p<0.02). Immunohistochemistry demonstrated a qualitative increase in MERTK protein expression on AM of smokers. Increased protein expression of MERTK on AM of smokers was confirmed by Western and flow analyses (p< 0.007 and p< 0.0002, respectively). MERTK, a cell surface receptor that recognizes apoptotic cells, is expressed on human AM, and its expression is up-regulated in AM of cigarette smokers. This may reflect an increased demand for removal of apoptotic cells in smokers, an observation with implications for the development of chronic obstructive pulmonary disease (COPD), a disorder associated with dysregulated apoptosis of lung parenchymal cells.
Publication Title
Overexpression of apoptotic cell removal receptor MERTK in alveolar macrophages of cigarette smokers.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This dataset is part of the manuscript titled "The metabolic regulator ERRalpha, a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cells intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer.
Publication Title
The metabolic regulator ERRĪ±, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
PKCe, an oncogenic member of the PKC family, is aberrantly overexpressed in epithelial cancers. To date, little is known about functional interactions of PKCe with other genetic alterations and the effectors of this kinase that contribute to its tumorigenic and metastatic phenotype. Here we demonstrate that PKCe cooperates with the loss of the tumor suppressor Pten for the development of prostate cancer in a mouse model. Mechanistic analysis revealed that PKCe overexpression and Pten loss individually and synergically cause a remarkable up-regulation in the production of the chemokine CXCL13. Notably, targeted disruption of CXCL13 or its receptor CXCR5 in prostate cancer cells impaired their migratory and tumorigenic properties. In addition to providing evidence for an autonomous vicious cycle driven by PKCe, our studies identified a compelling rationale for targeting the CXCL13:CXCR5 axis for prostate cancer treatment.
Publication Title
Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Medium conditioned by LLC cells stimulates thermogenic gene expression when added onto primary adipocytes. We generated single cell colonies from parental LLC cells. Media conditioned by the subclones stimulated thermogenic gene expression in primary adipocytes at varying degrees.
Publication Title
Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The Mediator complex is an evolutionary conserved multiprotein complex that plays an essential role in initiating and regulating transcription. Its function is to act as a universal adaptor between RNA Polymerase II and DNA-bound transcription factors to translate regulatory information from activators and repressors to the transcriptional machinery. We have found that the PFT1 gene (which encodes the MED25 subunit of the Mediator complex) is required for the uncompromised expression of both salicylic acid- and jasmonate-dependent defense genes as well as resistance to the leaf-infecting fungal pathogens, Alternaria brassicicola and Botrytis cinerea in Arabidopsis. Surprisingly, we found that the pft1/med25 mutant showed increased resistance to the root infecting pathogen Fusarium oxysporum and that this resistance was independent of classical defense genes. In addition, the over-expression of PFT1 led to increased susceptibility to F. oxysporum. Therefore, to explore this phenomenon further, we wished to use whole genome transcript profiling to identify which genes may be playing a role in pft1/med25-mediated resistance to F. oxysporum.
Publication Title
The mediator complex subunit PFT1 is a key regulator of jasmonate-dependent defense in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples