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GSE42726
Drosophila melanogaster
12 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Alphaviruses establish a persistent infection in arthropod vectors, which is essential for effective transmission of the virus to vertebrate hosts. The development of persistence in insects is not well understood, although it is thought to involve the innate immune response. Using a transgenic fly system (SINrep) expressing a self-replicating viral genome, we have previously demonstrated the antiviral response of the Drosophila Imd (Immune Deficiency) and Jak-STAT innate immunity pathways.
Publication Title
An antiviral role for antimicrobial peptides during the arthropod response to alphavirus replication.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of electron transport chain component, cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage dependent growth and acquired invasive phenotypes. Disruption of CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling, includes activation of PI3-kinase, IGF1R and Akt, Ca2+ sensitive transcription factors and also, TGF1, MMP16, periostin that are involved in oncogenic progression. Whole genome expression analysis showed up regulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mtDNA depletion, though distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in CcO complex can potentially induce tumor progression.
Publication Title
Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This dataset contains Affymetrix Mouse Genome 430 2.0 Array data obtained from K7M2 cells over-expressing ezrinT567A and the wild-type
Publication Title
Dysregulation of ezrin phosphorylation prevents metastasis and alters cellular metabolism in osteosarcoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Targeting components of the mitogen-activated protein kinase (MAPK) pathway prolongs survival of patients with advanced BRAFV600E melanomas but such an approach is not curative because of the rapid acquisition of numerous resistance mechanisms. Here we analyze melanoma cells that evade MAPK inhibitors by undergoing a senescence-like, slow-growth, phenotype, which leads to acquired resistance. The initial therapeutic response is characterized by an integrated stress response program, including stimulation of autophagic flux, activation of the endoplasmic reticulum machinery, and an enhanced ability of detoxifying reactive oxygen species. Reversibly senescent cells also exhibit an increase in mitochondrial genome copy number and a strong metabolic shift towards oxidative phosphorylation (OxPhos). Inducing mitochondrial dysfunction by co-targeting the MAPK pathway and mitochondrial Hsp90-directed protein folding with specific inhibitors prevented entry of cells into a reversibly senescent state, suppressed mitochondrial energy metabolism and augmented therapy response.
Publication Title
Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors.
Sample Metadata Fields
Disease, Disease stage, Cell line, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Insight into mechanisms controlling gene expression in the spermatogonial stem cell (SSC) will improve our understanding of the processes regulating spermatogenesis and aid in treating problems associated with male infertility.
Publication Title
Spermatogonial stem cell self-renewal requires ETV5-mediated downstream activation of Brachyury in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Expression of GDNF-regulated genes was studied in cultures of self-renewing rat spermatogonial stem cells established from 8-10 day old rat pups maintained in a defined serum free medium. GDNF is the primary regulator of spermatogonial stem cell self renewal in the rat.
Publication Title
Identification of glial cell line-derived neurotrophic factor-regulated genes important for spermatogonial stem cell self-renewal in the rat.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Diabetogenic CD8+ G9C8 clone cells and the T cells from a transgenic mouse bearing the same TCR as the clone, displayed differences in their ability to induce disease in vivo.Microarray analysis was done to identify the molecular basis for such differences between the two sets of CD8 T cells.
Publication Title
Cytotoxic mechanisms employed by mouse T cells to destroy pancreatic β-cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Self-renewal and differentiation of spermatogonial stem cells (SSCs) provides the foundation for testis homeostasis, yet mechanisms that control their functions in mammals are poorly defined. We used microarray transcript profiling to identify specific genes whose expression are augmented in the SSC-enriched Thy1+ germ cell fraction of mouse pup testes. Comparisons of gene expression in the Thy1+ germ cell fraction to the Thy1-depeleted testis cell population identified 202 genes that are expressed 10-fold or higher in Thy1+ cells. This database provided a mining tool to investigate specific characteristics of SSCs and identify novel mechanisms that potentially influence their functions.
Publication Title
Colony stimulating factor 1 is an extrinsic stimulator of mouse spermatogonial stem cell self-renewal.
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- Mus musculus
- 5 Downloadable Samples
- Illumina Genome Analyzer II
Description
MicroRNAs (miRs) play a key role in the control of gene expression in a wide array of tissue systems where their functions include the regulation of self-renewal, cellular differentiation, proliferation, and apoptosis. However, the functional importance of individual miRs in controlling spermatogonial stem cell (SSC) homeostasis has not been investigated. Using high-throughout sequencing, we profiled the expression of miRs in the Thy1+ testis cell population, which is highly enriched for SSCs, and the Thy1- cell population, composed primarily of testis somatic cells. In addition, we profiled the global expression of miRs in cultured germ cells, also enriched for SSCs. Our results demonstrate that miR-21, along with miR-34c, -182, -183, -146a, -465a-3p, -465b-3p, -465c-3p, and -465c-5p are preferentially expressed in the Thy1+ SSC-enriched population, as compared to Thy1- somatic cells, and we further observed that Thy1+ SSC-enriched testis cells and SSC-enriched cultured germ cells share remarkably similar miR expression profiles. Overall design: Spermatogonial Stem Cell enriched cell populations (freshly isolated and short-term cultured) and somatic cell populations were isolated from C57B/L6 mouse donors and subjected to small RNA isolation and sequencing.
Publication Title
MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples