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GSE13280
Homo sapiens
44 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionising radiation (IR)-induced DNA double strand breaks in 74 paediatric ALL patients. We found an apoptosis-resistant response in 36% of patients and an apoptosis-sensitive response in the remaining 64% of leukaemias. Global gene expression profiling of 11 apoptosis-resistant and 11 apoptosis-sensitive ALLs revealed abnormal up-regulation of multiple pro-survival pathways in response to IR in apoptosis-resistant leukaemias and differential post-transcriptional activation of the PI3-Akt pathway was observed in representative resistant cases. It is possible that abnormal pro-survival responses to DNA damage provide one of the mechanisms of primary resistance in ALL .
Publication Title
Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
Illumina HiSeq 2500
Description
The overall study (Quinn et al. Cell Reports, 2018) aimed to understand why CD8 virtual memory T (TVM) cells become markedly less proliferative in response to TCR-driven signals with increasing age, whereas CD8 true naive (TN) cells maintain their proliferative capacity. Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naïve CD8++ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Ageing also causes accumulation of antigen-naïve but semi-differentiated “virtual memory” (TVM) cells but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naïve T cells (TN cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naïve CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged TVM cells exhibit a profile consistent with senescence, marking the first description of senescence in an antigenically naïve T cell population. Overall design: In the RNA-Seq analysis uploaded here, we have sorted TN cells (CD44lo), TVM cells (CD49dlo CD44hi) and CD8 conventional memory T (TMEM) (CD49dhi CD44hi) cells from naive young mice (3 months old) or aged mice (18 months old). To sort enough cells of each type, we pooled 4 mice, so each replicate represents a pooled sample of 4 mice. Each replicate was split in half, with half the sample frozen in TRIzol immediately for our directly ex vivo or "unstim" sample and the other half of the sample stimulated with plate-bound anti-CD3 (10ug/mL), anti-CD8a (10ug/mL) and antiCD11a (5 ug/mL) and soluble recombinant human IL-2 (10U/mL) for 5 hours, before being frozen in TRIzol as our stimulated or "stim" samples. We therefore collected 2 replicates for each cell subsets (designated "1" and "2") and the "unstim" and "stim" samples are matched. Altogether, we had 24 samples (young (Y) and aged (A); replicate 1 and replicate 2, with cells pooled from 4 mice in each replicate; TN, TVM and TMEM cells; unstim and stim match across each replicate). Due to lane capacity limits for sequencing, we processed these samples for RNA and sequencing in two batches (Batch 1- Y1_Tn_Unstim, Y1_Tvm_Unstim, Y1_Tmem_Unstim, Y1_Tn_Stim, Y1_Tvm_Stim, Y1_Tmem_Stim, A1_Tn_Stim, A1_Tvm_Stim, A1_Tmem_Stim, A2_Tn_Stim, A2_Tvm_Stim, A2_Tmem_Stim. Batch 2- Y2_Tn_Unstim, Y2_Tvm_Unstim, Y2_Tmem_Unstim, Y2_Tn_Stim, Y2_Tvm_Stim, Y2_Tmem_Stim, A1_Tn_Unstim, A1_Tvm_Unstim, A1_Tmem_Unstim, A2_Tn_Unstim, A2_Tvm_Unstim, A2_Tmem_Unstim). Of note, in Batch 2 we ran a duplicate of Y1_Tn_Unstim (Y1_Tn_Unstim_norm) to test for any batch effect, but none was observed. Extracted RNA was treated with recombinant DNAse I (Roche) according to the manufacturer's instructions, purified using the RNeasy MinElute Cleanup columns (Qiagen) and analysed for RNA quality using the RNA 6000 Nano kit (Agilent) on an Agilent 2100 Bioanalyzer. Samples were prepared with the Illumina TruSeq RNA v2 sample preparation protocol (cDNA synthesis, adapter ligation, PCR amplification) (Illumina) and run using 100 bp paired end sequencing on an Illumina Hi-Seq. Adapters were trimmed with Trim Galore and trimmed reads were aligned to mm10 genome with TopHat2 version 2.1.1 (Kim et al., 2013) keeping the strand information. Only concordantly aligned read pairs were retained, duplicate fragments were removed using MarkDuplicates from Picard tools and read pairs with mapping quality less than 5 were discarded. To generate a counts matrix, retained read pairs were assigned to genes using featureCounts function (Liao et al., 2014) from Bioconductor Rsubread package taking into account strand information.
Publication Title
Metabolic characteristics of CD8<sup>+</sup> T cell subsets in young and aged individuals are not predictive of functionality.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We used microarrays to detail the global programme of gene expression in the fetal lung late in gestation, from mothers that had been fed normal chow, high fibre, or acetate in the drinking water. The experiment was designed to examine the hypothesis that metabolites of the mother i.e. acetate could cross the placenta and influence gene transcription in the fetus. Diets used were "Normal chow" (NC) (8720310), or "High-fiber" (SF11-025) (Specialty feeds, Perth, Australia. Acetate (200 mM) was provided in the drinking water and refreshed three times per week.
Publication Title
Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Infection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Publication Title
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
We provide data showing alternative splicing regulation by Muscleblind proteins in MEFs. MEFs lacking functional Muscleblind (DKO MEFs) were stably reconstituted with Muscleblind proteins from Homo sapiens, Ciona intestinalis, Drosophila melanogaster, Caenorhabditis elegans or Trichoplax adhaerens and splicing regulation was explored using RNA-seq analysis followed by MISO (Mixture of Isoforms). Overall design: Alternative splicing was accessed using RNA-sequencing data from five DKO MEF lines reconstituted with different GFP-tagged Muscleblind homologs or GFP alone and compared to RNA-seq data from three WT MEF lines and three control DKO MEFs (no Muscleblind reconstitution). A total of 12 samples were used for high-throughput sequencing.
Publication Title
Conservation of context-dependent splicing activity in distant Muscleblind homologs.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mice lacking the transcription factor Fezf1 exhibit defects in the structural and molecular organiztion of their olfactory system. To invetigate this at the level of gene expression, we isolated Fezf1 expressing cells by FACS from the MOE of Fezf1+/- or Fezf1-/- animals and compared their gene expression profiles.
Publication Title
Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: CHOP_1.0_ENTREZG (huex10st)
Description
Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease.
Publication Title
Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions.
Publication Title
Endurance exercise as a countermeasure for aging.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
We explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number burst-forming units-erythroid (BFU-E), while lenalidomide specifically increased colony-forming units-erythroid (CFU-E). Use of the drugs in combination demonstrates that their effects are not redundant.
Publication Title
Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation.
Publication Title
Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive regulator of cell proliferation via direct regulation of c-MYC.
Sample Metadata Fields
Cell line
View Samples