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GSE53546
Homo sapiens
10 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Nuclear lamin B1 constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of lamin B1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion; in addition we observed an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrate that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that lamin B1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S-phase due to activation of Chk1 and telomere attrition. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.
Publication Title
Loss of lamin B1 results in prolongation of S phase and decondensation of chromosome territories.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 42 Downloadable Samples
Illumina HiSeq 2500
Description
Transcriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat. Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen. To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control. Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). Overall design: There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.
Publication Title
A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Expression analysis of mature Arabidopsis trichomes in Col-0 and two mutants, triptychon (try-JC) and glabra3 (gl3-3)
Publication Title
Transcriptional profiling of mature Arabidopsis trichomes reveals that NOECK encodes the MIXTA-like transcriptional regulator MYB106.
Sample Metadata Fields
Specimen part
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- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray expression profiling has become a valuable tool in the evaluation of the genetic consequences of metabolic disease. Although 3-biased gene expression microarray platforms were the first generation to have widespread availability, newer platforms are gradually emerging that have more up-to-date content and/or higher cost efficiency. Deciphering the relative strengths and weaknesses of these various platforms for metabolic pathway level analyses can be daunting. We sought to determine the practical strengths and weaknesses of four leading commercially-available expression array platforms relative to biologic investigations, as well as assess the feasibility of cross-platform data integration for purposes of biochemical pathway analyses. METHODS: Liver RNA from B6.Alb/cre,Pdss2loxP/loxP mice having primary Coenzyme Q deficiency was extracted either at baseline or following treatment with an antioxidant/antihyperlipidemic agent, probucol. Target RNA samples were prepared and hybridized to Affymetrix 430 2.0, Affymetrix Gene 1.0 ST, Affymetrix Exon 1.0 ST, and Illumina Mouse WG-6 expression arrays. Probes on all platforms were re-mapped to coding sequences in the current version of the mouse genome. Data processing and statistical analysis were performed by R/Bioconductor functions, and pathway analyses were carried out by KEGG Atlas and GSEA. RESULTS: Expression measurements were generally consistent across platforms. However, intensive probe-level comparison suggested that differences in probe locations were a major source of inter-platform variance. In addition, genes expressed at low or intermediate levels had lower inter-platform reproducibility than highly expressed genes. All platforms showed similar patterns of differential expression between sample groups, with steroid biosynthesis consistently identified as the most down-regulated metabolic pathway by probucol treatment. CONCLUSIONS: This work offers a timely guide for metabolic disease investigators to enable informed end-user decisions regarding choice of expression microarray platform best-suited to specific research project goals. Successful cross-platform integration of biochemical pathway expression data is also demonstrated, especially for well-annotated and highly-expressed genes. However, integration of gene-level expression data is limited by individual platform probe design and the expression level of target genes. Cross-platform analyses of biochemical pathway data will require additional data processing and novel computational bioinformatics tools to address unique statistical challenges.
Publication Title
Cross-platform expression microarray performance in a mouse model of mitochondrial disease therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The only FDA approved therapy for Pompe is directed at correcting skeletal and cardiac muscle pathology, however, clinical and animal model data show strong histological evidence for a neurological disease component. While neuronal cell death and neuroinflammation are prominent in many lysosomal disorders, these processes have not been evaluated in Pompe disease. There is also no information available regarding the impact of Pompe disease on the fundamental pathways associated with synaptic communication.
Publication Title
Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates widespread neuropathology.
Sample Metadata Fields
Age
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Dynamical response to oxygen downshift under fermentation conditions was tested by taking sample before (S1) and after (S2, S3 and S4) the oxygen downshift. The dynamical changes relevant for ongoing research on physiology were applied.
Publication Title
Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 166 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T-cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. In this study, we performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN- to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlation between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.
Publication Title
Integrated Whole Genome and Transcriptome Analysis Identified a Therapeutic Minor Histocompatibility Antigen in a Splice Variant of ITGB2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Genome-wide gene expression was measured in peripheral blood mononuclear cells (PBMCs) from patients with cystic fibrosis (CF) after treatment in vitro with the flagellin protein fliC, and/or synthetic peptide IDR-1018 to assess patterns of gene expression. The patterns of gene expression suggest that CF cells have a hyperinflammatory phenotype including dysfunctional autophagy processes. The synthetic peptide IDR-1018 attentuates this hyperinflammatory phenotype. Overall design: Total RNA was obtained from PBMCs obtained from CF patients after treatment with the fliC flagellin protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.
Publication Title
Rescue of dysfunctional autophagy attenuates hyperinflammatory responses from cystic fibrosis cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defenses peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on macrophages/monocytes. Here we measured the effect of IDR-1018 on macrophage gene expression during differentiation. Differentiation in the presence of IDR-1018 induced a unique signature of immune responses suggesting that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. Overall design: RNA-seq was performed using the Illumina Genome Analyzer IIx platform. Monocytes were isolated from 3 healthy donors, and left unstimulated or stimulated for 4 hours with 20 µg/ml IDR-1018. For library preparation, 500 ng of total RNA was processed according to the Illumina TruSeq RNA sample preparation guide (Illumina catalogue number FC-122-1002). Briefly, mRNA was purified using poly-dT beads, followed by synthesis of the first and second cDNA strands, end repair addition of an poly-A overhang, and ligation of adapters and unique barcodes, as per the manufacturer’s instructions. DNA enrichment was carried out via a 15-cycle PCR. Following quantification, 8 pM of dsDNA was used for cluster generation on a CBOT instrument (Illumina, San Diego, CA). RNA sequencing was done on a GAIIx instrument (Illumina), performed as a single read run with 51 amplification cycles. Data processing was carried out in house, using CASAVA to convert raw data and demultiplex to FASTQ sequence files. Reads were aligned to the reference genome using TOPHAT, and then mapped to genes using the Bioconductor package GenomeRanges.
Publication Title
Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples