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GSE36168
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The PI3K/Akt signaling pathway impacts various aspects of CD8 T cell homeostasis, such as effect versus memory cell differentiation, during viral infection. We used microarrays to determine which downstream molecules were affected and what other signaling pathways were interconnected with the Akt pathway by constitutive activation of Akt in LCMV-infected CD8 T cells.
Publication Title
Signal integration by Akt regulates CD8 T cell effector and memory differentiation.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 43 Downloadable Samples
Illumina HiSeq 2000
Description
Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer’s disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia. Overall design: Role of Fmn2 gene for PTSD like phenotypes and impairments of synaptic plasticity.
Publication Title
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cellular senescence is a program of irreversible cell cycle arrest that normal cells undergo in response to progressive shortening of telomeres, changes in telomeric structure, oncogene activation or oxidative stress. The underlying signalling pathways, potentially of major clinicopathological relevance, are unknown. A major stumbling block to studying senescence has been the absence of suitable model systems because of the asynchrony of this process in heterogeneous cell populations. To simplify this process many investigators study oncogene-induced senescence due to expression of activated oncogenes where senescence occurs prematurely without telomere attrition and can be induced acutely in a variety of cell types. We have taken a different approach by making use of the finding that reconstitution of telomerase activity by introduction of the catalytic subunit of human telomerase alone is incapable of immortalising all human somatic cells, but inactivation of the p16-pRB and p53-p21 pathways are required in addition. The ability of SV40 large T antigen to inactivate the p16-pRB and p53-p21 pathways has enabled us to use a thermolabile mutant of LT antigen, in conjunction with hTERT, to develop conditionally immortalised human (HMF3A) fibroblasts that are immortal but undergo an irreversible growth arrest when the thermolabile LT antigen is inactivated leading to activation of pRB and p53. When these cells cease dividing, senescence-associated- b-galactosidase activity is induced and the growth-arrested cells have morphological features and express genes in common with senescent cells. Since these cells growth arrest in a synchronous manner they are an excellent starting point for dissecting the pathways that underlie cellular senescence and act downstream of p16-pRB and p53-p21 pathways. We have combined genome-wide expression profiling with genetic complementation to undertake identification of genes that are differentially expressed when these conditionally immortalised human fibroblasts undergo senescence upon activation of the p16-pRB and p53-p21 tumour suppressor pathways.
Publication Title
Activation of nuclear factor-kappa B signalling promotes cellular senescence.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 48 Downloadable Samples
- NextSeq 500
Description
Liver X Receptors (LXRa and ß) are ligand-activated transcription factors that play a key role in the control of lipid homeostasis, as well as modulation of immunity and inflammation. Besides ligand binding, LXR activity can be regulated by posttranslational modifications, such as phosphorylation. This study aims to assess changes in bone marrow derived macrophage transcriptional profiles of mice that carry LysMcre directed phosphorylation deficient-version of LXRa compared (S196A) to wild-type (WT). Overall design: BMDM mRNA profiles of either LdlrKO or M-LXRa-S196A-LdlrKO male mice after being fed a Western diet for 12 weeks. 12 samples, 4 groups, in triplicate: (1) LdlrKO basal, (2) LdlrKO+ ligand, (3) M-LXRa-S196A-LdlrKO basal, (4) M-LXRa-S196A-LdlrKO+ligand
Publication Title
Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 285 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This series represents 180 lymph-node negative relapse free patients and 106 lymph-node negate patients that developed a distant metastasis.
Publication Title
Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 41 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin 8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
Publication Title
Identification of a gene regulatory network associated with prion replication.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite the significant reduction in the overall burden of cardiovascular disease (CVD) over the past decade, CVD still accounts for a third of all deaths in the United States and worldwide each year. While efforts to identify and reduce risk factors for atherosclerotic heart disease (i.e. hypertension, dyslipidemia, diabetes mellitus, cigarette smoking, inactivity) remain the focus of primary prevention, the inability to accurately and temporally predict acute myocardial infarction (AMI) impairs our ability to further improve patient outcomes. Our diagnostic evaluation for the presence of coronary artery disease relies on functional testing, which detects flow-limiting coronary stenosis, but we have known for decades that most lesions underlying AMI are only of mild to moderate luminal narrowings, not obstructing coronary blood flow. Accordingly, there is a dire need of improved diagnostics for underlying arterial plaque dynamics, fissure and rupture. Here we describe the designation of a specific gene expression pattern acting as a molecular signature for acute myocardial infarction present in whole blood of patients that was determined using microarray analysis of enriched circulating endothelial cells (CEC).
Publication Title
A Whole Blood Molecular Signature for Acute Myocardial Infarction.
Sample Metadata Fields
Specimen part, Disease
View Samples