Filters
Technology
Platform
GSE67589
Homo sapiens
56 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background
Publication Title
Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite wide scale vaccination with Mycobacterium bovis BCG, the prevalence of tuberculosis remains high, reflecting the global variable efficacy of this vaccine against adult pulmonary TB. Characterisation of different immune responses to M. tuberculosis and M. bovis BCG would increase understanding of pathology following M. tuberculosis infection or reactivation, and would facilitate the rational design of a new vaccine. Gene expression profiling was conducted on samples from diluted whole blood cultures from three healthy donors following incubation with live mycobacteria for six days. Approximately 8,000 gene entities were at least two-fold up- or down- regulated by the mycobacteria, and both mycobacteria induced similar expression changes in approximately 2,300 genes. Strikingly, many genes exhibited qualitatively different expression patterns, with over 1,000 genes up-regulated in response to M. bovis BCG but not changed by M. tuberculosis. Gene Ontology analysis revealed that the genes which failed to upregulate in M. tuberculosis-infected cultures included a large proportion of genes with lysosomal function. The inhibited up-regulation of expression of IFN--inducible protein 30, acid phosphatase 2, cathepsin B and GM2 ganglioside activator was verified in samples from six biologically independent donors by qRT-PCR. The failure to up-regulate these genes in response to M. tuberculosis may constitute an immune evasion mechanism, preventing intracellular killing and antigen presentation.
Publication Title
Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 129 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background Accurate assessment of treatment efficacy would facilitate clinical trials of new anti-tuberculosis drugs. TB patients exhibit altered peripheral immunity which reverts during successful treatment. We hypothesised that these changes could be observed in whole blood transcriptome profiles. Methods Ex vivo blood samples from 27 pulmonary TB patients were assayed at diagnosis and during conventional treatment. RNA was processed and hybridised to Affymetrix GeneChips, to determine expression of over 47,000 transcripts. Findings There were significant changes in expression of over 4,000 genes during treatment. Rapid, large scale changes were detected, with down-regulated expression of ~1,000 genes within the first week, including inflammatory markers such as the complement components C1q and C2. This was followed by slower changes in expression of different networks of genes, including a later increase in expression of B cell markers, transcription factors and signalling molecules. Interpretation The expression of many genes is drastically altered during TB disease, with components of the humoral immune response being markedly affected. The treatment-induced restoration reflects the simultaneous suppression and activation of different immune responses in TB. The rapid initial down-regulation of expression of inflammatory mediators coincides with rapid killing of actively dividing bacilli, whereas slower delayed changes occur as drugs act on dormant bacilli and as lung pathology resolves. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity.
Publication Title
Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response.
Sample Metadata Fields
Specimen part, Disease, Subject, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background Accurate assessment of treatment efficacy would facilitate clinical trials of new anti-tuberculosis drugs. TB patients exhibit altered peripheral immunity which reverts during successful treatment. We hypothesised that these changes could be observed in whole blood transcriptome profiles. Methods Ex vivo blood samples from 27 pulmonary TB patients were assayed at diagnosis and during conventional treatment. RNA was processed and hybridised to Affymetrix GeneChips, to determine expression of over 47,000 transcripts. Findings There were significant changes in expression of over 4,000 genes during treatment. Rapid, large scale changes were detected, with down-regulated expression of ~1,000 genes within the first week, including inflammatory markers such as the complement components C1q and C2. This was followed by slower changes in expression of different networks of genes, including a later increase in expression of B cell markers, transcription factors and signalling molecules. Interpretation The expression of many genes is drastically altered during TB disease, with components of the humoral immune response being markedly affected. The treatment-induced restoration reflects the simultaneous suppression and activation of different immune responses in TB. The rapid initial down-regulation of expression of inflammatory mediators coincides with rapid killing of actively dividing bacilli, whereas slower delayed changes occur as drugs act on dormant bacilli and as lung pathology resolves. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity.
Publication Title
Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 909 Downloadable Samples
Illumina HiSeq 2000
Description
Identification of blood biomarkers that prospectively predict Mycobacterium tuberculosis treatment response. Overall design: There are a total of 914 samples used in this design. This involves samples from 100 cases and 38 controls. Most of the samples have 2 technical replicates where as 2 samples have 4. Samples from the TB cases have been collected on the start day of TB treatment and on 1,4 and 24 weeks after treatment as well. For some subjects we also have samples after the subject has been cured. The case or TB Subjects have been categorized by the nature of their response as definite,probable or possible cure. The day of cure is presented in the time to negativity column. Also provided in the metadata are the MGIT -Mycobacteria Growth Indicator Tube and XPERT (cartridge based nucleic acid amplification test, automated diagnostic test that can identify Mycobacterium tuberculosis (MTB)) values at the various times of sample collection for all TB Subjects.
Publication Title
Host blood RNA signatures predict the outcome of tuberculosis treatment.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Signaling by the cytokine LIF and its downstream transcription factor, STAT3, prevents differentiation of pluripotent embryonic stem cells (ESCs) by opposing MAP kinase signaling. This contrasts with most cell types where STAT3 signaling induces differentiation. We find that STAT3 binding across the pluripotent genome is dependent upon Brg, the ATPase subunit of a specialized chromatin remodeling complex (esBAF) found in ESCs. Brg is required to establish chromatin accessibility at STAT3 binding targets, in essence preparing these sites to respond to LIF signaling. Moreover, Brg deletion leads to rapid Polycomb (PcG) binding and H3K27me3-mediated silencing of many Brg-activated targets genome-wide, including the target genes of the LIF signaling pathway. Hence, one crucial role of Brg in ESCs involves its ability to potentiate LIF signaling by opposing PcG. Contrary to expectations, Brg also facilitates PcG function at classical PcG target including all four Hox loci, reinforcing their repression in ESCs. These findings reveal that esBAF does not simply antagonize PcG, but rather, the two chromatin regulators act both antagonistically and synergistically with the common goal of supporting pluripotency.
Publication Title
esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function.
Sample Metadata Fields
Cell line, Treatment
View Samples- Caenorhabditis elegans
- 23 Downloadable Samples
- Affymetrix C. elegans Gene 1.1 ST Array
Description
Temperature, as a universal enviromental factor, has prolonged effect on physiological and pathological functions of different species. In order to expolore the temperol effect of temperature on C.elegans longevity, we used microarray to check the whole-genome expression profiling of L4 larvae and Day3-old adults of C.elegans maintaining at different temperature
Publication Title
Environmental Temperature Differentially Modulates C. elegans Longevity through a Thermosensitive TRP Channel.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Distinctive SWI/SNF-like ATP-dependent chromatin remodeling esBAF complexes are indispensable for the maintenance and pluripotency of mouse embryonic stem (ES) cells. To understand the mechanism underlying the roles of these complexes in ES cells, we performed high-resolution genome-wide mapping of the core ATPase subunit, Brg, using ChIP-Seq technology. We find that that esBAF, as represented by Brg, binds to genes encoding components of the core ES transcriptional circuitry, including Polycomb group proteins. esBAF colocalizes extensively with Oct4, Sox2 and Nanog genome-wide, and shows distinct functional interactions with Oct4 and Sox2 at its target genes. Surprisingly, no significant colocalization of esBAF with PRC2 complexes, represented by Suz12, is observed. Lastly, esBAF co-binds with Stat3 and Smad1 genome-wide, consistent with a direct and critical role in LIF and BMP signaling essential to maintain pluripotency. Taken together, our studies indicate that esBAF is both an essential component of the core pluripotency transcriptional network, and might also be a critical component of the LIF and BMP signaling pathways essential for maintenance of self-renewal and pluripotency.
Publication Title
An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes. Overall design: Strand-specific total RNA-Seq analysis in wild-type (WT) and dal80-delta (dal80) cells grown in glutamine- and/or proline-containing medium.
Publication Title
Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Characterized by striking metastatic propensity and chemoresistance, melanoma is among the most lethal cutaneous malignancies. The transcription factor ATF2 was shown to elicit oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, a mouse model engineered to express a transcriptionally inactive form of Atf2 (Atf2?8,9) was found to be sufficient to induce nevi formation and, when crossed with BrafV600E animals, to promote melanoma development. The cross of Atf2?8,9 with BrafV600E;Pten-/- mice augmented pigmentation, tumorigenicity, and metastasis. Similar to mouse Atf2?8,9, the human ATF2 splice variant 5 enhanced growth and migration capacity of cultured melanoma and immortalized melanocytes. Induced Melan-A, CXCL9, S100A8, CCR7 expression, seen in Atf2?8,9-driven tumors associate with their enhanced pigmentation, immune infiltration and propensity to metastasize. Notably, elevated ATF2SV5 expression in melanoma specimens coincided with poor prognosis. The gain-of-function activity elicited by the truncated ATF2 form offers unexpected insight into mechanisms underlying melanoma development and progression. Overall design: Compared silencing of ATF2SV5 in H3A cells vs. silencing of ATF2WT via Ampliseq whole transcriptome analysis on the Ion Proton
Publication Title
A Transcriptionally Inactive ATF2 Variant Drives Melanomagenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples