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Mus musculus
308 Downloadable Samples
Illumina HiSeq 2500
Description
One of sleep's putative functions is mediation of adaptation to waking experiences. Chronic stress is a common waking experience, however, which specific aspect of sleep is most responsive, and how sleep changes relate to behavioral disturbances and molecular correlates remain unknown. We quantified sleep, physical, endocrine, and behavioral variables, as well as the brain and blood transcriptome in mice exposed to 9 weeks of unpredictable chronic mild stress (UCMS). Comparing 46 phenotypical variables revealed that rapid-eye-movement sleep (REMS), corticosterone regulation, and coat state were most responsive to UCMS. REMS theta oscillations were enhanced, whereas delta oscillations in non-REMS were unaffected. Transcripts affected by UCMS in the prefrontal cortex, hippocampus, hypothalamus, and blood were associated with inflammatory and immune responses. A machine-learning approach controlling for unspecific UCMS effects identified transcriptomic predictor sets for REMS parameters that were enriched in 193 pathways, including some involved in stem cells, immune response, apoptosis, and survival. Only three pathways were enriched in predictor sets for non-REMS. Transcriptomic predictor sets for variation in REMS continuity and theta activity shared many pathways with corticosterone regulation, in particular pathways implicated in apoptosis and survival, including mitochondrial apoptotic machinery. Predictor sets for REMS, and anhedonia shared pathways involved in oxidative stress, cell proliferation, and apoptosis. These data identify REMS as a core and early element of the response to chronic stress, and identify apoptosis and survival pathways as a putative mechanism by which REMS may mediate the response to stressful waking experiences. Overall design: Study of transcriptomic changes in three stress- and sleep-related brain regions (prefrontal cortex, hippocampus, hypothalamus) and blood following 9 weeks of Unpredictable Chronic Mild Stress (UCMS) in mice.
Publication Title
REM sleep's unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Bos taurus
- 87 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNA regulation of the bovine local and systemic monocyte transcriptional responses to an in vivo Streptococcus uberis challenge Overall design: Milk and blood isolated CD14+ monocyte cells taken from 5 infected Holstein friesians and 5 control Holstein friesians. Five animal infected with live S. uberis, cells extracted at 0, 12, 24, 36, and 48 hours post infection.
Publication Title
MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Bos taurus
- 94 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs are amplifiers of monocyte inflammatory networks and repressors of metabolism Overall design: Milk and blood isolated CD14+ monocyte cells taken from 5 infected Holstein friesians and 5 control Holstein friesians. Five animal infected with live S. uberis, cells extracted at 0, 12, 24, 36, and 48 hours post infection.
Publication Title
MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 483 Downloadable Samples
- NextSeq 500
Description
Rare heterozygous coding variants in the triggering receptor expressed in myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer''s disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell-type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity. We primarily discovered changes in an endothelial gene-enriched subnetwork at 4 months, including a shift toward a more central role for the amyloid precursor protein gene, coupled with widespread disruption of other cell-type subnetworks, including a subnetwork with neuronal identity. We reveal an unexpected potential role of Trem2 in the homeostasis of endothelial cells that goes beyond its known functions as a microglial receptor and signaling hub, suggesting an underlying link between immune response and vascular disease in dementia. Methods: We performed differential expression and co-expression network analysis on a RNA-Seq profiled Trem2 knockout (KO) mouse using two brain areas sampled at 4- and 8-months to obtain a systems level view of the effects of the absence of Trem2. Results: The absence of Trem2 has a stronger effect at an earlier age with the number of differential expressed (DE) genes being 17-fold greater at 4 months than at 8 months in cortex. By integrating DE genes and network analysis, we discovered gene clusters associated with the disruption of blood vessel formation at 4 months of age and protein targeting primarily affecting the hippocampus at 8 months. Further integration of cell type and ontology information revealed a large disruption of a gene module enriched for endothelial cell markers coinciding with the module enriched for neuron cell markers having weaker connections to modules with oligodendrocyte and astrocyte identities. The module with neuronal identity has decreased expression only in the KO where it has closer association with a new module enriched for phagocytic functions. Conclusions: Combining gene co-expression and differential expression analysis on a newly generated RNA-Seq profiled Trem2 KO mouse demonstrate that the absence of Trem2 produces a disruption which mainly affects endothelialon related processes at 4 months of age. It results in a ripple effect that disrupts the cross-talk of other cell types at 8 months, including reduced expression of a gene module enriched in neuron related functions and a shift towards a more central role for App. This study reveals an unexpected role of Trem2 in the homeostasis of endothelial cells that goes beyond its known functions as a microglial receptor and signaling hub suggesting new paths for investigation at the intersection between Trem2, Alzheimer's disease and vascular dementia. Overall design: Hippocampus and cortex were selected because they represent tissues affected in AD at early and late stages, respectively (Matarin 2015, Mastrangelo 2008). Brain tissue samples were obtained from male Trem2 knockout (KO) and wild type (WT) control mice at two time points: 4 months and 8 months. These time points span the onset and late disease stages in well established AD mouse models (Matarin 2015). RNA-Seq was used to profile the transcriptomes for each sample. Two technical replicates were obtained for each sample.
Publication Title
Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 3000
Description
Metabolic engagement is intrinsic to immune cell function. Prostaglandin E2 (PGE2) has been shown to modulate macrophage activation, yet how PGE2 might affect metabolism is unclear. Here we show that PGE2 causes mitochondrial membrane potential (??m) to dissipate in interleukin-4 activated macrophages (M(IL-4)). Effects on ??m are a consequence of PGE2-initiated transcriptional regulation of genes in the malate-aspartate shuttle (MAS), particularly GOT1. Reduced ??m causes alterations in the expression of 126 voltage regulated genes (VRGs) including Resistin like molecule-a (RELMa), a key marker of M(IL-4), and genes that regulate cell cycle. The transcription factor ETS variant 1 (ETV1) plays a role in the regulation of 38% of the VRGs. These results reveal ETV1 as a ??m-sensitive transcription factor, and ??m as a mediator of mitochondrial-directed nuclear gene expression. Overall design: RNA-seq was performed on bone marrow derived macrophages (triplicate) exposed to IL-4 alone or in combination with PGE2 or Valinomycin plus no stimulation controls. In addition, RNA-seq was performed on bone marrow derived macrophages stimulated in the same way as before, however the transcription factor ETV1 was knocked down.
Publication Title
Mitochondrial Membrane Potential Regulates Nuclear Gene Expression in Macrophages Exposed to Prostaglandin E2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 27 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Deregulated expression of the Myc transcription factor is a frequent causal mutation in human cancer. Thousands of putative Myc target genes have been identified in in vitro studies, indicating that Myc exerts highly pleiotropic effects within cells and tissues. However, the complexity and diversity of Myc gene targets has confounded attempts at identifying which of these genes are the critical targets mediating Myc-driven tumorigenesis in vivo. Acute activation of Myc in a reversibly switchable transgenic model of Myc-mediated cell tumorigenesis induces rapid tumor onset whereas subsequent Myc de-activation triggers equally rapid tumor regression. Thus, sustained Myc activity is required for tumor maintenance. We have used this reversibly switchable kinetic tumor model in combination with high-density oligonucleotide microarrays to develop an unbiased strategy for identifying candidate Myc-regulated genes responsible for maintenance of Myc-dependent tumors. Consistent with known Myc functions, some Myc-regulated genes are involved in cell growth, cycle and proliferation. In addition, however, many Myc-regulated genes are specific to cells, indicating that a significant component of Myc action is cell-type specific. Finally, we identify a very restricted cadre of genes whose expression is inversely regulated upon Myc activation-induced tumor progression and de-activation-induced tumor regression. By definition, such genes are candidates for tumor maintenance functions. Combining reversibly switchable, transgenic models of tumor formation and regression with genomic profiling offers a novel strategy with which to deconvolute the complexities of oncogenic signaling pathways in vivo
Publication Title
Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A novel mouse line was found to exhibit prominent mechanosensory deficits both behaviorally and at the primary sensory afferents, and exhibits decreased ATP release from the skin.
Publication Title
Mechanosensory and ATP Release Deficits following Keratin14-Cre-Mediated TRPA1 Deletion Despite Absence of TRPA1 in Murine Keratinocytes.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Recent evidence supports a role for RNA as a common pathogenic agent in both the polyglutamine and untranslated dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcripts as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease associated repeat sequences - CAG, CUG and AUUCU - were specifically expressed in the neurons of Drosophila and resultant common, early, transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3- signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.
Publication Title
Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.
Sample Metadata Fields
Sex, Age, Specimen part
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GSE3185- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Summary: Astrocytomas can be categorized as either low grade or high grade (glioblastoma). Low grade astrocytomas are not generally aggressive tumors whereas glioblastomas are and in turn have a high mortality rate. The purpose of this experiment is to identify genetic differences between the two types.
Publication Title
Overexpression of the EGFR/FKBP12/HIF-2alpha pathway identified in childhood astrocytomas by angiogenesis gene profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Ewing sarcoma family of tumors (ESFT) are aggressive bone and soft tissue tumors of unknown cellular origin. Most ESFT express EWS-FLI1, a chimeric protein which functions as a growth-promoting oncogene in ESFT but is toxic to most normal cells. A major difficulty in understanding EWS-FLI1 function has been the lack of an adequate model in which to study EWS-FLI1-induced transformation. Although the cell of origin of ESFT remains elusive, both mesenchymal (MSC) and neural crest (NCSC) have been implicated. We recently developed the tools to generate NCSC from human embryonic stem cells (hNCSC). In the current study we used this model to test the hypothesis that neural crest-derived stem cells are the cells of origin of ESFT and to evaluate the consequences of EWS-FLI1 expression on human neural crest biology.
Publication Title
Modeling initiation of Ewing sarcoma in human neural crest cells.
Sample Metadata Fields
Specimen part
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