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GSE36782
Homo sapiens
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gliomas are the most devastating of primary adult malignant brain tumors. These tumors are highly infiltrative and can arise from cells with extensive self-renewal capability and chemoresistance, frequently termed glioma-propagating cells (GPCs). GPCs are thus the plausible culprits of tumor recurrence. Treatment strategies that eradicate GPCs will greatly improve disease outcome. Such findings support the use of GPCs as in vitro cellular systems for small molecule screening. However, the nuances in utilizing GPCs as a cellular screening platform are not trivial. These slow-growing cells are typically cultured as suspension, spheroid structures in serum-free condition supplemented with growth factors. Consequently, replenishment of growth factors throughout the screening period must occur to maintain cells in their undifferentiated state, as the more lineage-committed, differentiated cells are less tumorigenic. We will present a case study of a small molecule screen conducted with GPCs and explain how unique sphere activity assays were implemented to distinguish drug efficacies against the long-term, self-renewing fraction, as opposed to transient-amplifying progenitors, latter of which are detected in conventional viability assays. We identified Pololike kinase 1 as a regulator of GPC survival. Finally, we leveraged on public glioma databases to illustrate GPC contribution to disease progression and patient survival outcome.
Publication Title
Glioma-propagating cells as an in vitro screening platform: PLK1 as a case study.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
Publication Title
Parkin pathway activation mitigates glioma cell proliferation and predicts patient survival.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2000
Description
Bone marrow derived macrophages were infected with Listeria monocytogenes for 4 hours. We investigated differently expressed genes in the absence of DDX3X upon infection and also in steady state conditions. Overall design: Investigation of gene expression in wt and Ddx3x deficient bone marrow derived macrophages in response to Listeria monocytogenes infection.
Publication Title
The RNA helicase DDX3X is an essential mediator of innate antimicrobial immunity.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation.
Publication Title
Genomic analysis of reactive astrogliosis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This study provides the dectin-1 and NFAT responsive genes for 2h and 4h of curdlan treatment.
Publication Title
NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 15 Downloadable Samples
- Bovine Gene 1.1 ST Array (bovgene11st)
Description
Steer mesenteric fat transcriptome.
Publication Title
Relationships between the genes expressed in the mesenteric adipose tissue of beef cattle and feed intake and gain.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Dendritic cells (DCs) are crucial for sensing pathogens and triggering immune response. GM-CSF myeloid dendritic cells (GM-DCs) secrete several cytokines including IL-2 upon activation by pathogen associated molecular pattern (PAMP) ligands. DC IL-2 has been shown to be important for innate and adaptive immune responses, however its importance in DC physiology has never been demonstrated. This is due to ambiguity in expression of the CD122 subunit of the IL-2 trimeric receptor complex crucial for signaling. We show here that autocrine IL-2 signaling is functional in GM-DCs in early time window of stimulation with PAMPs. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexs at the cell surface. Autocrine IL-2 signaling inhibits survival of PAMP matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest immune regulation by a novel autocrine signaling pathway that can potentially be exploited in DC immunotherapy.
Publication Title
Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The generation of nave T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a nave T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.
Publication Title
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The generation of nave T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a nave T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.
Publication Title
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Sample Metadata Fields
Specimen part
View Samples