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GSE13493
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection.
Publication Title
PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and a major health problem in the United States. While the cytokine TGF-ß has been implicated in PDAC development, it can exert bot pro- and anti-tumorigenic effects that are highly context dependent and incompletely understood. To better characterize the responses of neoplastic pancreas cells to TGF-ß, three-dimensional (3D) cultures of KrasG12D-expressing mouse pancreatic epithelial cells were employed. While active exposure to exogenous TGF-ß caused the KrasG12D cells to growth arrest, its subsequent removal allowed the cells to enter a hyper-proliferative, quasi-mesenchymal (QM) and progenitor-like state. This transition was highly stable and maintained by autocrine TGF-ß signaling. Transient pulses of TGF-ß have been observed during pancreatitis, a major risk factor for PDAC, and may therefore serve to convert pre-existing KrasG12D-expressing cells into QM cells. While untreated KrasG12D cells formed simple cysts in vivo, QM cells formed ductal structures resembling human PanINs. Furthermore, markers of the QM state are expressed in human PDAC and are associated with worse outcomes. These data suggest that the QM state plays a role in PDAC development and may selectively contribute to more aggressive PDAC subtypes. This work therefore provides novel molecular insights into both PDAC development and the complex role of TGF-ß in tumorigenesis. Overall design: Three technical replicates per experimental group from one isolate were analyzed by RNA sequencing
Publication Title
Pre-neoplastic pancreas cells enter a partially mesenchymal state following transient TGF-β exposure.
Sample Metadata Fields
Subject
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
The animal piRNA pathway is a small RNA silencing system that acts in gonads and protects the genome against the deleterious influence of transposons. A major bottleneck in the field is the lack of comprehensive knowledge of the factors and molecular processes that constitute this pathway. We conducted an RNAi screen in Drosophila and identified ~50 genes that strongly impact the ovarian somatic piRNA pathway. Many identified genes fall into functional categories that indicate essential roles for mitochondrial metabolism, RNA export, the nuclear pore, transcription elongation and chromatin regulation in the pathway. Follow-up studies on two factors demonstrate the identification of components acting at distinct hierarchical levels of the pathway. Finally, we define CG2183/Gasz as a novel primary piRNA biogenesis factor in somatic and germline cells. Based on the similarities between insect and vertebrate piRNA pathways our results have far-reaching implications for the understanding of this conserved genome defense system. Overall design: Steady-state RNA levels in wild-type ovarian somatic cells (OSC) and RNAi knock-downs of the piRNA pathway components.
Publication Title
The genetic makeup of the Drosophila piRNA pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study we examined whether -1,3 glucans are masked by surface proteins in Pneumocystis, and what role -glucans play in Pneumocystis-associated inflammation. For 3 species, including P. jirovecii, which causes Pneumocystis pneumonia (PCP) in humans, P. carinii, and P. murina, -1,3 glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using Q-PCR and microarray techniques, we demonstrated in a mouse model of PCP that treatment with caspofungin, an inhibitor of -1,3 glucan synthesis, for 21 days, decreased expression of a broad panel of inflammatory markers, including IFN-, TNF-, IL-1, IL-6, and multiple chemokines/chemokine ligands. Thus, -glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.
Publication Title
β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences.
Publication Title
Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors.
Publication Title
Characterization of distinct immunophenotypes across pediatric brain tumor types.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Congenital glioblastoma multiforme (cGBM) historically has been considered an aggressive tumor of infancy requiring extensive chemotherapy to achieve cure. We report on 4 patients at our institution with cGBMs who were treated with surgery and chemotherapy (carboplatin and etoposide every 21 days for 2-6 cycles). Four of four patients are progression free at a median time of 27.5 months (22-103 months). To characterize the molecular biology of cGBM, we compared the gene expression profiles of 3 cGBMs to 12 pediatric and 6 primary adult glioblastomas collected at our institution. Unsupervised hierarchical clustering showed cGBMs grouped together with other high-grade gliomas. cGBMs demonstrated marked similarity to both pediatric and adult GBMs, with only a total of 31 differentially expressed genes identified (FDR < 0.05). Unique molecular features of congenital GBMs identified included over-expression of multiple genes involved in glucose metabolism and tissue hypoxia pathways. Four tyrosine kinases were also mong the up-regulated genes (RET, RASGRF2, EFNA5, ALK). Thus, at our institution congenital GBMs, while similar both histologically and molecularly to other GBMs, appear to have a good prognosis with surgery in combination with relatively moderate chemotherapy. Further study is needed to determine if the few gene expression differences that were identified may contribute to the better survival seen in these tumors compared to pediatric or adult GBMs.
Publication Title
Clinical and molecular characteristics of congenital glioblastoma.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ependymoma, the 3rd most common brain tumor in children, recurs in approximately 50% of patients. There is currently no robust marker that predicts for recurrence, which is a significant clinical problem
Publication Title
Immune gene and cell enrichment is associated with a good prognosis in ependymoma.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
PIWI proteins and their bound piRNAs form the core of a gonad specific small RNA silencing pathway in animals that protects the genome against the deleterious activity of transposable elements. Recent studies linked the piRNA pathway to TUDOR biology, where TUDOR domains of various proteins recognize and bind symmetrically methylated Arginine residues in PIWI proteins. We systematically analyzed the Drosophila TUDOR protein family and identified three previously not characterized TUDOR domain-containing genes (CG4771, CG14303 and CG11133) as essential piRNA pathway members. We characterized CG4771 (Avocado) in detail and demonstrate a critical role for this protein during primary piRNA biogenesis in somatic and germline cells of the ovary. Avocado physically and/or genetically interacts with the primary pathway components Piwi, Armitage, Yb and Zucchini. Avocado also interacts with the Tdrd12 orthologs CG11133 and CG31755, which are essential for primary piRNA biogenesis in the germline and probably functionally replace the related and soma specific factor Yb. Overall design: small RNA libraries were prepared from total RNA isolation of 8 different genotypes
Publication Title
A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Introduction: Pediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive brain tumor that arises from the sellar/suprasellar region. Despite a high survival rate with current surgical and radiation therapy (75-95% at 10 years), ACP is associated with debilitating visual, endocrine, neurocognitive and psychological morbidity, resulting in exceptionally poor quality of life for survivors. Identification of an effective pharmacological therapy would drastically decrease morbidity and improve long term outcomes for children with ACP.
Publication Title
Identification of targets for rational pharmacological therapy in childhood craniopharyngioma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples