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SRP112551
Homo sapiens
49 Downloadable Samples
Description
Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group). DeSeq2 identified 35 genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted P<0.1). In depression, altered genes include humanin-like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted P<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted P<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorder Overall design: We examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in the dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden death medication-free individuals post mortem. Using small RNA-seq, we also examined miRNA expression (nine samples per group).
Publication Title
Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Toxoplasma strains are known to inhibit the expression of several interferon-gamma induced genes, and a type II strain was shown to dysregulate genome-wide responses to interferon-gamma in human fibroblasts (Kim et al., 2007, J Immunol.). In this study we aimed to determine the effect of infection with three clonal lineages of Toxoplasma, type I, II, and III strains on genome-wide interferon-gamma induced transcription in murine macrophages. We also assessed the effect of the two main Toxoplasma modulators of mouse macrophage transcription, ROP16 and GRA15 (Jensen et al., 2011, Cell Host Microbe).
Publication Title
Toxoplasma gondii clonal strains all inhibit STAT1 transcriptional activity but polymorphic effectors differentially modulate IFNγ induced gene expression and STAT1 phosphorylation.
Sample Metadata Fields
Specimen part
View Samples- Equus caballus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptomic analysis of ICM and TE from in vivo-derived equine blastocysts using Illumina sequencing technology Overall design: RNA was extracted from individual equine blastocyst ICM and TE (Arcturus Picopure), cDNA was synthesized and amplified (Nugen Ovation V2) and indexed libraries were created for sequencing (TruSeq DNA V1)
Publication Title
RNA-seq transcriptome profiling of equine inner cell mass and trophectoderm.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II) consists of repeated YSPTSPS heptapeptides and connects transcription with cotranscriptional events. Threonine-4 (Thr4) of the CTD repeats has been shown to function in histone mRNA 3'-end processing in chicken cells and in transcriptional elongation in human cells. Here, we demonstrate that, in budding yeast, Thr4, although dispensable for growth in rich media, is essential in phosphate-depleted or galactose-containing media. Thr4 is required to maintain repression of phosphate-regulated (PHO) genes under normal growth conditions and for full induction of PHO5 and the galactose-induced GAL1 and GAL7 genes. We identify genetic links between Thr4 and the histone variant Htz1 and show that Thr4, as well as the Ino80 chromatin remodeler, is required for activation-associated eviction of Htz1 specifically from promoters of the Thr4-dependent genes. Our study uncovers a connection between transcription and chromatin remodeling linked by Thr4 of the CTD. Overall design: RNA-seq of wild type and T4V mutant of budding yeast RNAP II CTD in duplicates
Publication Title
Threonine-4 of the budding yeast RNAP II CTD couples transcription with Htz1-mediated chromatin remodeling.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Homo sapiens
- 38 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix Human Genome U133A Array (hgu133a)
Description
Toxoplasma strains have been shown to modulate host cell transcription. We have found a type II Toxoplasma gene, GRA15, which activates the nuclear translocation of the NF-kappaB p65 transcription factor.
Publication Title
Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: genemapperhumanexon1.0cdf_3.0 (huex10st)
Description
The data presented is intended to analyse the changes in the expression profiles of human MSCs (Mesenchymal Stromal/Stem Cells) associated to different tissue specific stimulus.
Publication Title
Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Toxoplasma strains have been shown to modulate host cell transcription. We have found a type II Toxoplasma gene, GRA15, which activates the nuclear translocation of the NF-kappaB p65 transcription factor.
Publication Title
Strain-specific activation of the NF-kappaB pathway by GRA15, a novel Toxoplasma gondii dense granule protein.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative mRNA splicing represents an effective mechanism of regulating gene function and is a key element to increase the coding capacity of the human genome. Today, an increasing number of reports illustrates that aberrant splicing events are common and functionally important for cancer development. However, more comprehensive analyses are warranted to get novel insights into the biology underlying malignancies like e.g. acute myeloid leukemia (AML). Here, we performed a genome-wide screening of splicing events in AML using an exon microarray platform. We analyzed complex karyotype and core binding factor (CBF) AML cases (n=64) in order to evaluate the ability to detect alternative splicing events distinguishing distinct leukemia subgroups. Testing different commercial and open source software tools to compare the respective AML subgroups, we could identify a large number of potentially alternatively spliced transcripts with a certain overlap of the different approaches. Selected candidates were further investigated by PCR and sequence analysis: out of 24 candidate genes studied, we could confirm alternative splice forms in 8 genes of potential pathogenic relevance, such as PRMT1 regulating transcription through histone methylation and participating in DNA damage response, and PTPN6, which encodes for a negative regulator of cell cycle control and apoptosis. In summary, this first large Exon microarray based study demonstrates that transcriptome splicing analysis in AML is feasible but challenging, in particular with regard to the currently available software solutions. Nevertheless, our results show that alternatively spliced candidate genes can be detected, and we provide a guide how to approach such analyses.
Publication Title
A robust estimation of exon expression to identify alternative spliced genes applied to human tissues and cancer samples.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Although liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, including Nanog mRNA, which modulate exit from the proliferative stem-cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. Overall design: RNA-sequencing of polyA selected RNA molecules in NTera2/D1 cells and Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq).
Publication Title
DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples