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GSE12218
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Robust type I interferon (IFN-alpha/beta) production in plasmacytoid dendritic cells (pDCs) is critical for anti-viral immunity. Here we demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or the downstream mediators of mTOR p70S6K1,2 kinases during pDC activation via Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and the subsequent activation of interferon response factor 7 (IRF7), resulting in impaired IFN-alpha production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed anti-viral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in a diminution of IFN-alpha production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling plays a critical role in TLR-mediated IFN-alpha responses by pDCs.
Publication Title
Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 87 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Human Genome U133 A 2.0 Custom CDF Version 9
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 87 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs. The immune responses generated by YF-17D by profiling 20,077 genes in 25 vaccine recipients were accessed at days 1, 3, 7, and 21 post-vaccination compared to pre-vaccination in PBMCs.
Publication Title
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Sample Metadata Fields
Time
View Samples- Rattus norvegicus
- 128 Downloadable Samples
IonTorrentProton
Description
The current study employed next-generation RNA sequencing to examine gene expression related to brain aging and cognitive decline. Young and aged rats were trained on a spatial episodic memory task. Hippocampal regions CA1, CA3 and the dentate gyrus (DG) were isolated. Poly-A mRNA was examined using two different platforms, Illumina and Ion Proton. The Illumina platform was used to generate lists of genes that were differentially expressed across regions, ages, and in association with cognitive function. The gene lists were then retested using the Ion Proton platform. The results describe regional differences in gene expression and point to regional differences in vulnerability to aging. Aging was associated with increased expression of immune response related genes, particularly in the dentate gyrus. Finally, for the memory task used, impaired performance of aged animals was linked to the regulation of Ca2+ and synaptic function in region CA1. Overall design: The study contains a total of 10 young (5-6 months) and 24 aged (17-22 months) Fischer 344 male rats which were used to investigate expression patterns associated with aging and behavior. Prior to gene analysis, the animals were characterized on an episodic memory task across two academic institutions to test the reliability of the task (University of Florida: 5 young rats and 13 aged rats; University of Arizona: 5 young rats and 11 aged rats). Following total RNA isolation for the CA1, CA3 and DG regions, next-generation sequencing (NGS) libraries were prepared for two platforms, Illumina and Ion Proton. For both platforms, poly-A selection of mRNA was performed followed by library preparation protocols for each NGS system. In addition, whole transcriptome sequencing in Illumina was also performed using the ribominus method to investigate differential expression of additional RNA species across the hippocampus. This Series includes only the samples examined using the Ion Proton platform.
Publication Title
Hippocampal Transcriptomic Profiles: Subfield Vulnerability to Age and Cognitive Impairment.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 92 Downloadable Samples
- Illumina HiSeq 2500
Description
The current study employed next generation RNA sequencing using two different platforms (Illumina and Ion Proton) to examine gene expression differences related to brain aging, cognitive decline, and hippocampus subregions (CA1, CA3, DG). Young and aged rats were trained on a spatial episodic memory task. The results describe regional differences in gene expression and point to regional differences in vulnerability to aging. Aging was associated with increased expression of immune response related genes, particularly in the dentate gyrus. For the memory task, impaired performance of aged animals was linked to the regulation of Ca2+ and synaptic function in region CA1. Finally, we provided a transcriptomic characterization of the three subregions regardless of age or cognitive status, highlighting and confirming a correspondence between cytoarchitectural boundaries and molecular profiling. Overall design: Male Fisher 344 rats of two ages, young (5-6 months, total n = 10; n = 5 AZ, n = 5 FL) and aged (17-22 months, total n = 24; n = 11 AZ, n = 13 FL) were obtained from National Institute on Aging''s colonies (Taconic, FL; Charles River, AZ). Animals were maintained on a 12:12 hour light/dark schedule, and provided ad libitum access to food and water prior to the set shifting task. The Morris Water Maze test was conducted, and behavioural data were acquired with either Noldus EthoVision computer tracking software (Noldus Information Technology, (Leesburg, VA) in FL or AnyMaze (Wood Dale, IL) in AZ) and included path-length and time in the goal and opposite quadrants. Two weeks following water maze testing, rats were anesthetized with isoflurane (Piramal Healthcare), decapitated and the brain was rapidly removed. The hippocampus was isolated, a 1-2 mm slice was removed from the dorsal hippocampus, and the CA1, CA3 and dentate gyrus (DG) regions were dissected [1, 8]. The collected tissue was immediately frozen in liquid nitrogen and stored in -80ºC until processed.
Publication Title
Hippocampal Transcriptomic Profiles: Subfield Vulnerability to Age and Cognitive Impairment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Precociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. Here we present evidence that prostate cancer stem-like cells (CSC) can be found in histopathologically negative prostate draining lymph nodes (PDLN) in mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). PDLN-derived CSC were phenotypically and functionally identical to CSC obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. CSC derived from either PDLN or mPIN used the extracellular matrix protein Tenascin-C (TNC) to inhibit T cell receptor-dependent T cell activation, proliferation and cytokine production. Mechanistically, TNC interacted with 51 integrin on the cell surface of T cells, inhibiting reorganization of the actin-based cytoskeleton therein required for proper T cell activation. CSC from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in PDLN upon mPIN development. CXCR4 was critical for the development of PDLN-derived CSC, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Taken together, our work establishes a pivotal role for TNC in tuning the local immune response to establish equilibrium between disseminated nodal CSC and the immune system.
Publication Title
Tenascin-C Protects Cancer Stem-like Cells from Immune Surveillance by Arresting T-cell Activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
In order to identify genes regulated by VE-cadherin expression, we compared a mouse VE-cadherin null cell line (VEC null) with the same line reconstituted with VE-cadherin wild type cDNA (VEC positive). The morphological and functional properties of these cell lines were described previously [Lampugnani,M.G. et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J. Cell Biol. 161, 793-804 (2003)]. By Affymetrix gene expression analysis we found several genes up-regulated by VE-cadherin, among which claudin-5 reached remarkably high levels. The up-regulation of these genes required not only VE-cadherin expression but also cell confluence suggesting that VE-cadherin clustering at junctions was needed.
Publication Title
Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
During limb development, fibroblast growth factors (FGFs) govern proximal-distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal-distal and anterior-posterior axes by maintaining sonic hedgehog (SHH) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. SHH, in turn, maintains FGFs in the apical ectodermal ridge (AER) which caps the distal tip of the limb bud. Crosstalk between FGF and SHH signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well characterized.
Publication Title
LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Oncogene-induced DNA methylation-mediated transcriptional silencing of tumor suppressors frequently occurs in cancer, but the mechanism and functional role of this silencing in oncogenesis is not fully understood. Here, we show that oncogenic epidermal growth factor receptor (EGFR) induces silencing of multiple unrelated tumor suppressors in lung adenocarcinomas and glioblastomas by inhibiting DNA demethylase TET oncogene family member 1 (TET1) via the C/EBP transcription factor. After oncogenic EGFR inhibition, TET1 binds to tumor suppressor promoters and induces their re-expression via active DNA demethylation. Ectopic expression of TET1 potently inhibits lung and glioblastoma tumor growth, and TET1 knockdown confers resistance to EGFR inhibitors in lung cancer cells. Lung cancer samples exhibited reduced TET1 expression or TET1 cytoplasmic localization in a majority of cases. Collectively, these results identify a conserved pathway of oncogenic EGFR-induced DNA methylation-mediated transcriptional silencing of tumor suppressors, which may have therapeutic benefit for oncogenic EGFR-mediated lung cancers and glioblastomas.
Publication Title
Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples