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GSE22282
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dendritic cells (DCs) are professional antigen-presenting cells whose activity is intrinsically linked to the microenvironment. Hypoxia is a condition of low oxygen tension occurring in inflammatory tissues that creates a special microenvironment conditioning cell physiology. We studied the effects of hypoxia on the differentiation of human monocytes into DCs and maturation into mature DCs. Mature DCs were differentiated in vitro from human monocytes under normoxic or hypoxic conditions and the gene expression profile was determined.
Publication Title
Hypoxia modulates the gene expression profile of immunoregulatory receptors in human mature dendritic cells: identification of TREM-1 as a novel hypoxic marker in vitro and in vivo.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia, which characterizes most tumor tissues, can alter the function of different immune cell types, favoring tumor escape mechanisms. In this study, we show that hypoxia profoundly acts on NK cells by influencing their transcriptome, affecting their immunoregulatory functions, and changing the chemiotactic responses of different NK cell subsets.
Publication Title
Hypoxia Modifies the Transcriptome of Human NK Cells, Modulates Their Immunoregulatory Profile, and Influences NK Cell Subset Migration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaGenomeAnalyzerII
Description
Abstract: Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP protein SmB/B’ self-regulates its expression by promoting the inclusion of a highly-conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B’ in human cells results in reduced levels of snRNPs and in a striking reduction in the inclusion levels of hundreds of alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors. Overall design: HeLa cells were transfected with a control non-targeting siRNA pool (siNT), or with siRNA pools designed to knockdown SmB/B'' or SRSF1 (also known as SF2/ASF/SFRS1). Sequence reads were aligned to exon-exon junction sequences in a database of EST/cDNA-mined cassette-type alternative splicing events. Processed data files (.bed and .txt) provided as supplementary files on the Series record. Processed data file build information: hg18.
Publication Title
Regulation of alternative splicing by the core spliceosomal machinery.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Escherichia coli release Extracellular Vesicles (EVs) which carry diverse molecular cargo. Pathogenic E.coli EVs contain virulence factors which assist during infection in the host in different mechanisms.The RNA cargo of E.coli EVs has not been assessed in their effect in the host. We used microarray data to asses and compare the global response of bladder cells to EV-RNA from pathogenic E.coli (Uropathogenic UPEC 536) and non-pathogenic E. coli (probiotic Nissle 1917)
Publication Title
Effect of the Extracellular Vesicle RNA Cargo From Uropathogenic <i>Escherichia coli</i> on Bladder Cells.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Maggot ES is known to induce wound healing in vivo to improve chronic wound repair. The effects have been studies at the protein and molecular level but never before at the transcriptional level.
Publication Title
The transcriptional responses of cultured wound cells to the excretions and secretions of medicinal Lucilia sericata larvae.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. Here, we demonstrate a direct role for histone modifications in alternative splicing. We find distinctive histone modification signatures which correlate with splicing outcome in a set of human genes. Modulation of histone modifications causes splice site switching. The mechanism for histone-mediated splice site selection involves a histone mark which is read by a chromatin protein, which in turn recruits a splicing regulator. These results outline an adaptor system for reading of histone marks by the pre-mRNA splicing machinery. Overall design: To obtain an estimate of how many PTB-dependent alternative splicing events are regulated by SET2/MRG15-mediated recruitment of PTB, we carried out a genomewide comparative analysis of alternative splicing in hMSC cells depleted of either SETD2, MRG15 or PTB using specific siRNAs, or mock-depleted using a control siRNA.
Publication Title
Regulation of alternative splicing by histone modifications.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- NextSeq 500
Description
We did the RNA-seq analysis to examine the global impact of Nicotinamide (NAM) on hiPSC-derived RPE transcriptome in order to better understand the mechanism of action of NAM. NAM inhibited the expression of Age related Macular degeneration (AMD) associated protein transcripts in hiPSC-derived RPE. Overall design: Seven hiPSC-RPE lines (4 AMD donors and 3 Control donors) that had been cultured with 10mM NAM or vehicle for three weeks were used for RNA extraction and RNA-seq analysis. We treated 4 AMD hiPSC-RPE and 3 Control hiPSC-RPE lines with 10mM NAM or vehicle.
Publication Title
Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 79 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Autism spectrum disorder (ASD) is a common, highly heritable neuro-developmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an etiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1/FOX1, and a module enriched for immune genes and glial markers. Using high-throughput RNA-sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in ASD brain. Moreover, using a published autism GWAS dataset, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic etiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder.
Publication Title
Transcriptomic analysis of autistic brain reveals convergent molecular pathology.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 41 Downloadable Samples
- Illumina HiSeq 4000
Description
The rate of RNA Polymerase II (RNAPII) elongation has an important role in the control of Alternative splicing (AS); however, the in vivo consequences of an altered elongation rate are unknown. Here, we generated mouse embryonic stem cells (ESCs) knocked-in for a slow elongating form of RNAPII. We show that a reduced transcriptional elongation rate results in early embryonic lethality in mice and impairs the differentiation of ESCs into the neural lineage. This is accompanied by changes in splicing and in gene expression in ESCs and along the pathway of neuronal differentiation. In particular, we found a crucial role for RNAPII elongation rate in transcription and splicing of long neuronal genes involved in synapse signaling. The impact of the kinetic coupling of RNAPII elongation rate with AS is more predominant in ESC-differentiated neurons than in pluripotent cells. Our results demonstrate the requirement for an appropriate transcriptional elongation rate to ensure proper gene expression and to regulate AS during development. Overall design: 4sURDB-Seq mouse wt and homozygous Polr2a[R749H] mutant embryonic stem cells in triplicates.
Publication Title
A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. Overall design: To identify potential A2BP1-dependent differential splicing events in ASD brain, we performed high-throughput RNA sequencing (RNA-Seq) on three autism samples with significant downregulation of A2BP1 (average fold change by quantitative RT-PCR = 5.9) and three control samples with average A2BP1 levels. The list of potential A2BP1-depending differential splicing events in ASD is given in the Supplementary file linked at the foot of this record.
Publication Title
Transcriptomic analysis of autistic brain reveals convergent molecular pathology.
Sample Metadata Fields
No sample metadata fields
View Samples