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GSE8668
Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Relatively brief bouts of exercise alter gene expression in peripheral blood mononuclear cells (PBMCs), but whether or not exercise changes gene expression in circulating neutrophils (whose numbers, like PBMCs, increase) is not known. We hypothesized that exercise would activate neutrophil genes involved in apoptosis, inflammation, and cell growth and repair, since these functions in leukocytes are known to be influenced by exercise. Blood was sampled before and immediately after 30-min of constant, heavy (about 80% peak O2 uptake) cycle-ergometer exercise in 12 healthy men (19-29 yr old) of average fitness. Neutrophils were isolated using density gradients; RNA was hybridized to Affymetrix U133+2 Genechip arrays. Using FDR<0.05 with 95% confidence a total of 526 genes were differentially expressed between before and after exercise. 316 genes had higher expression after exercise. The Jak/STAT pathway, known to inhibit apoptosis, was significantly activated (EASE score, p<0.005), but 14 genes were altered in a way likely to accelerate apoptosis as well. Similarly, both proinflammatory (e.g., IL32, TNFSF8 and CCR5) and anti-inflammatory (e.g., ANXA1) were affected. Growth and repair genes like AREG and FGF2 receptor genes (involved in angiogenesis) were also activated. Finally, a number of neutrophil genes known to be involved in pathological conditions like asthma and arthritis were altered by exercise, suggesting novel links between physical activity and disease or its prevention. In summary, brief heavy exercise leads to a previously unknown substantial and significant alteration in neutrophil gene expression.
Publication Title
Effects of 30 min of aerobic exercise on gene expression in human neutrophils.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
miR-155 transgenic mice develop pre-B cell leukemia/lymphoma. Though some targets of miR-155 are known, understanding of the mechanism by which miR-155 overexpression drives malignant transformation is not known. MicroRNAs regulate multiple genes.
Publication Title
miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Eμ-miR-155 transgenic mouse model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 56 Downloadable Samples
IlluminaHiSeq2000
Description
Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses. Overall design: PBMC and six purified cell types from two vaccinated donors were isolated prior to (d0) and at days 1, 3, and 7 post-TIV vaccination for RNA-seq analysis
Publication Title
A cell-based systems biology assessment of human blood to monitor immune responses after influenza vaccination.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 44 Downloadable Samples
Description
Extracellular RNAs (exRNAs) in blood and other biofluids have attracted great interest as potential biomarkers in liquid biopsy applications, as well as for their potential biological functions. Whereas it is well-established that extracellular microRNAs are present in human blood circulation, the degree to which messenger RNAs (mRNA) and long noncoding RNAs (lncRNA) are represented in plasma is less clear. Here we report that mRNA and lncRNA species are present as small fragments in plasma that are not detected by standard small RNA-seq methods, because they lack 5'-phosphorylation or carry 3'-phosphorylation. We developed a modified sequencing protocol (termed "phospho-sRNA-seq") that incorporates upfront RNA treatment with T4 polynucleotide kinase (which also has 3' phosphatase activity) and compared it to a standard small RNA-seq protocol, using as input both a pool of synthetic RNAs with diverse 5' and 3' end chemistries, as well exRNA isolated from human blood plasma. Using a custom, high-stringency pipeline for data analysis we identified mRNA and lncRNA transcriptome fingerprints in plasma, including multiple tissue-specific gene sets. In a longitudinal study of hematopoietic stem cell transplant (HSCT) patients, we found different sets corresponding to bone marrow- and liver- enriched genes, which tracked with bone marrow recovery or liver injury, providing proof-of-concept validation of this method as a biomarker approach. By accessing a previously unexplored realm of mRNA and lncRNA fragments in blood plasma, phospho-sRNA-seq opens up a new space for plasma transcriptome-based biomarker development in diverse clinical settings. Overall design: ExRNA-seq libraries were prepared from platelet-poor plasma obtained from serial blood draws collected from two individuals undergoing bone marrow transplantation. A total of 11 samples were collected from each individual, starting prior to chemotherapy/ratiation treatment (approximately 7 days pre-HSCT) the day of transplant, and then weekly up to approximately Day 63.
Publication Title
Phospho-RNA-seq: a modified small RNA-seq method that reveals circulating mRNA and lncRNA fragments as potential biomarkers in human plasma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
To investigate differential gene expression, we analyzed the entire transcriptomes of tumor and matched normal brain tissues obtained from a patient who had glioblastoma multiforme. We extracted and sequenced the mRNA using Illumina GA2 platform. The raw data was analyzed using our recently developed program called RNASEQR, as well as ERANGE, MapSplice, SpliceMap, and TopHat. Overall design: Tumor and matched control brain tissues were obtained from a Han-Chinese patient.
Publication Title
RNASEQR--a streamlined and accurate RNA-seq sequence analysis program.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The type III RNase Dicer is responsible for the maturation and function of microRNA (miRNA) molecules in the cell. It is now well documented that Dicer and the fine-tuning of the miRNA gene network are important for neuronal integrity. However, the underlying mechanisms involved in neuronal death, particularly in the adult brain, remain poorly defined. Here, we show that absence of Dicer in the adult forebrain is accompanied by a mixed neurodegenerative phenotype. While neuronal loss is observed in the hippocampus, cellular shrinkage is predominant in the cortex. Interestingly, neuronal degeneration coincides with the hyperphosphorylation of endogenous tau at several epitopes previously associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 as one of the candidate kinases responsible for this event in vivo. We further demonstrate that miRNAs belonging to the miR-15 family are potent regulators of ERK1 expression in mouse neuronal cells and co-expressed with ERK1/2 in vivo. Last, we show that miR-15a is specifically downregulated in Alzheimers disease brain. In sum, these results support the hypothesis that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation.
Publication Title
Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Mutations in GRIN2B are associated with intellectual disability in humans. We generated iPSC derived mature cortical neurons with mutations in GRIN2B and compared them to isogenic control cells. We found that both loss of function (LOF) and reduced dosage (RD) mutations in GRIN2B lead to reduced expression of NMDAR genes and increased expression of marker of immaturity, including KI67 and MET. Overall design: Examination of transcriptome in iPSC-derved mature neurons with and without the presence of mutations in GRIN2B
Publication Title
Disruption of GRIN2B Impairs Differentiation in Human Neurons.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The mechanisms and molecular pathways underlying interstitial lung diseases (ILDs) are poorly understood. Systems biology approaches were used to identify perturbed networks in these disease states to gain a better understanding of the underlying mechanisms of disease. Through profiling genes and miRNAs, we found subsets of genes and miRNAs that distinguish different disease stages, ILDs from controls, and idiopathic pulmonary fibrosis (IPF) from non-specific interstitial pneumonitis (NSIP). Traditional pathway analysis revealed several disease-associated modules involving genes from the TGF-beta, Wnt, focal adhesion and smooth muscle actin pathways that may be involved in advancing fibrosis.
Publication Title
Systems biology of interstitial lung diseases: integration of mRNA and microRNA expression changes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Molecular mechanisms controlling specification and differentiation of distinct neuron subtypes in the cerebral cortex are not well understood. Corticothalamic projection neurons (CThPN) are a diverse set of neurons, critical for function of the neocortex, but little is known about the molecular mechansims controlling their development.
Publication Title
Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity.
Sample Metadata Fields
Specimen part
View Samples