The goal of these studies was to determine the effects of fasting on skeletal muscle mRNA levels in healthy human subjects.
mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass.
Sex, Age, Specimen part, Treatment, Subject
View SamplesThis SuperSeries is composed of the SCANB SubSeries listed below.
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.
Specimen part
View SamplesBreast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival. To address these challenges, the Sweden Cancerome Analysis Network - Breast (SCAN-B) consortium was initiated in 2010 as a multicenter prospective study with longsighted aims to 1) analyze breast cancers with next-generation genomic technologies for translational research in a population-based manner and integrated with healthcare; 2) decipher fundamental tumor biology from these analyses; 3) utilize genomic data to develop and validate new clinically-actionable biomarker assays; and 4) build the infrastructure for real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing on the Illumina platform. In the three years from August 30, 2010 through August 31, 2013, we have consented and enrolled 3,979 patients with primary breast cancer at the seven hospital sites in South Sweden, representing approximately 85% of eligible patients in the catchment area. Pre-operative blood samples have been collected for 3,942 (99%) patients and primary tumor specimens collected for 2,929 (74%) patients. Herein we describe the study infrastructure and present initial proof of concept results from prospective RNA-sequencing including tumor molecular subtyping and detection of driver gene mutations. We demonstrate that large-scale population-based collection and RNA-sequencing analysis of breast cancer is feasible. The SCAN-B Initiative should significantly reduce the time to discovery, validation, and clinical implementation of novel molecular diagnostic and predictive tests. We welcome the participation of additional comprehensive cancer treatment centers.
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function.
Specimen part, Subject
View SamplesThe mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we have described the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins following cytomegalovirus (CMV) infection. The absence of B and myeloid cell-related signaling protein expression in these NK cell subsets correlated with promoter DNA hypermethylation. Genome-wide DNA methylation patterns were strikingly similar between CMV-associated adaptive NK cells and cytotoxic effector T cells, but differed from those of canonical NK cells. Functional interrogation demonstrated altered cytokine responsiveness in adaptive NK cells that was linked to reduced expression of the transcription factor PLZF. Furthermore, subsets of adaptive NK cells demonstrated significantly reduced functional responses to activated autologous T cells. The present results uncover a spectrum of epigenetically unique adaptive NK cell subsets that diversify in response to viral infection and have distinct functional capabilities compared to canonical NK cell subsets.
Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS).
Specimen part, Disease, Disease stage
View SamplesMicroRNAs are small noncoding RNA molecules that are involved in the control of gene expression. To investigate the role of microRNA in multiple sclerosis (MS), we performed global microarray analyses of mRNA and microRNA in peripheral blood T-cells from relapsing-remitting MS patients and controls. We identified 2,452 regulated genes and 21 regulated microRNA that differed between MS patients and controls. By Kolmogorov-Smirnov test, 20 of 21 regulated microRNA were shown to affect the expression of their target genes, many of which are involved in the immune system. LIGHT (TNFSF14) was a microRNA target gene significantly decreased in MS. The down-regulation of mir-494 and predicted mRNA-target LIGHT was verified by real-time PCR and we could demonstrate decreased serum levels of LIGHT in MS. Thus, regulated microRNA were significantly associated with both gene and protein expression of a molecule in immunological pathways. These findings indicate that microRNA may be important regulatory molecules in T-cells in MS.
MicroRNA regulate immune pathways in T-cells in multiple sclerosis (MS).
Specimen part, Disease, Disease stage
View SamplesMicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand-receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function. Overall design: Three RNA samples containing bilateral entire hippocampi from three different mice, per group. Group 1 were injected with vector containing GFP and a miR34sp/miR9sp and the other group were subjected to a vector expressing GFP only.
Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons.
No sample metadata fields
View SamplesWe established a neuron-specific Argonaute2:GFP-RNA immunoprecipitation followed by high throughput sequencing (AGO2-RIP-seq) to analyse the regulatory role of miRNAs in mouse hippocampal neurons. Using this technique, we identified more than two thousand miRNA target genes in hippocampal neurons, regulating essential neuronal features such as axon guidance and transcription. Furthermore, we found that stable inhibition of the highly expressed miR-124 in hippocampal neurons led to significant changes in the AGO2 binding of target mRNAs, resulting in subsequent upregulation of numerous miRNA target genes. Our data suggest that target redundancies are common among microRNA families. Together, these findings greatly enhance our understanding of the mechanisms and dynamics through which miRNAs regulate their target genes in neurons. Overall design: Analysis of the miRNA targetome in hippocampal neurons after inhibition of 2 different miRNAs. AAV5 injections into the hippocampus of adult C57BL/6 mice producing either of the following under a synapsin promoter: GFP only (Samples beginning with ''GFP124…'' or ''GFP125…''), GFP-miR124sp (Samples beginning with ''miR124…''), GFP-miR125sp (Samples beginning with ''miR125…''), GFP-AGO2-miR292sponge (samples ending with ''…292''), GFP-AGO2-miR124sponge (samples ending with ''…124''), GFP-AGO2-miR125sponge (samples ending with ''…125''). All other samples were sham-injected.
Identification of the miRNA targetome in hippocampal neurons using RIP-seq.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification and validation of single-sample breast cancer radiosensitivity gene expression predictors.
No sample metadata fields
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