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GSE1124
Homo sapiens
47 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
We aimed at finding differently expressed genes in whole blood cells of African children with asymptomatic Plasmodium falciparum infection (A), uncomplicated malaria (U), severe malarial anemia (A) and cerebral malaria (Ce) compared one to another and to healthy children (Co).
Publication Title
The blood transcriptome of childhood malaria.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Objective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38-controlled transcripts comprising female- and male-specific gene modules, with greater p38 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS
Publication Title
Sex-specific control of central nervous system autoimmunity by p38 mitogen-activated protein kinase signaling in myeloid cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
ISWI is an evolutionary conserved ATPase that catalyzes nucleosome remodeling in several different complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, have specialized functions despite their high similarity. Due to the lack of reagents the functions of SN2L in human cells had not been established. Newly established specific monoclonal antibodies and selective RNA interference protocols now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. Contrasting earlier results obtained in the mouse model, we found SNF2L broadly expressed in primary human tissues. Depletion of SNF2L in HeLa cells led to enhanced proliferation, morphological alterations and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. High levels of SNF2L expression in normal melanocytes contrast to undetectable expression in malignant melanoma. In summary, our data document an anti-correlation between SNF2L expression and several features characteristic of malignant cells.
Publication Title
Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.
Sample Metadata Fields
Cell line
View Samples- Sus scrofa
- 16 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The molecular mechanism underlying cardiac remodeling following myocardial infarction have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine.
Publication Title
Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The genome of Epstein-Barr virus (EBV) encodes 86 proteins but only a limited set is expressed in EBV-growth transformed B cells, termed lymphoblastoid cell lines (LCLs). These cells proliferate via the concerted action of EBV nuclear antigens (EBNAs) and latent membrane proteins (LMPs), some of which are rate limiting to establish a stable homeostasis of growth promoting and anti-apoptotic activities. We show here that EBV mutants, which lack the EBNA-3A gene, are impaired but can still initiate cell-cycle entry and proliferation of primary human B cells in contrast to an EBNA-2-deficient mutant virus. Surprisingly and in contrast to previous reports, these viral mutants are attenuated in growth transformation assays but give rise to permanently growing EBNA-3A negative B cell lines which exhibit reduced proliferation rates and elevated levels of apoptosis. Expression profiles of EBNA-3A deficient LCLs are characterized by 129 upregulated and 167 downregulated genes, which are significantly enriched for genes involved in apoptotic processes or cell cycle progression like the tumor suppressor gene p16/INK4A or might contribute to essential steps in the viral life cycle. In addition EBNA-3A cellular target genes remarkably overlap with previously identified targets of EBNA-2.
Publication Title
Differential gene expression patterns of EBV infected EBNA-3A positive and negative human B lymphocytes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Constitutive activation of the Wnt pathway leads to adenoma formation, an obligatory step towards intestinal cancer. In view of the established role of Wnt in regulating stemness, we attempted the isolation of cancer stem cells (CSCs) from Apc- and Apc/KRAS-mutant intestinal tumours. Whereas CSCs are present in malignant Apc/KRASmutant carcinomas, they appear to be very rare (<10-6) in the benign Apcmutant adenomas. In contrast, the Lin-CD24hiCD29+ subpopulation of adenocarcinoma cells appear to be enriched in CSCs with increased levels of active -catenin. Expression profiling analysis of the CSC-enriched subpopulation confirmed their enhanced Wnt activity and revealed additional differential expression of other signalling pathways, growth factor binding proteins, and extracellular matrix components. As expected, genes characteristic of the Paneth cell lineage (e.g. defensins) are co-expressed together with stem cell genes (e.g. Lgr5) within the CSC-enriched subpopulation. This is of interest as it may indicate a cancer stem cell niche role for tumor-derived Paneth-like cells, similar to their role in supporting Lgr5+ stem cells in the normal intestinal crypt. Overall, our results indicate that oncogenic KRAS activation in Apc-driven tumours results in the expansion of the CSCs compartment by increasing b-catenin intracellular stabilization.
Publication Title
Cancer stemness in Apc- vs. Apc/KRAS-driven intestinal tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Understanding the DNA elements that constitute and control the regulatory genome is critical for the appropriate therapeutic management of complex diseases. Here, using chromosome Y (ChrY) consomic mouse strains on the C57BL/6J background, we show that susceptibility to two diverse animal models of autoimmune disease, including experimental allergic encephalomyelitis (EAE) and experimental myocarditis, correlates with the natural variation in copy number of Sly and Rbmy multicopy ChrY genes. In the B6 background, ChrY possesses gene regulatory properties that impact both genome-wide gene expression and the presence of alternative splice variants in pathogenic CD4+ T cells. Using a ChrY consomic strain on the SJL background, we discovered a preference for ChrY-mediated gene regulation in macrophages, the immune cell subset underlying the EAE sexual dimorphism in SJL mice, rather than CD4+ T cells. Importantly, in both genetic backgrounds, an inverse correlation exists between the number of Sly and Rbmy ChrY gene copies and the number of significantly upregulated genes in immune cells, thereby supporting a link between copy number variation of Sly and Rbmy with the ChrY genetic element exerting regulatory properties. Moreover, in humans, an analysis of the CD4+ T cell transcriptome from male multiple sclerosis patients versus healthy controls provides further evidence for an evolutionarily conserved mechanism of gene regulation by ChrY. Thus, these data establish ChrY as a member of the regulatory genome in mammals due to its ability to regulate gene expression and alternative splicing in immune cells linked to disease.
Publication Title
The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Small regulatory RNAs including small interfering RNAs (siRNAs) and microRNAs (miRNAs) guide Argonaute (Ago) proteins to specific target RNAs leading to mRNA destabilization or translational repression. We recently reported the identification of Importin 8 (Imp8) as a novel component of miRNA-guided regulatory pathways. Imp8 interacts with Ago proteins and localizes to cytoplasmic processing bodies (P-bodies), structures involved in RNA metabolism. For this micro-array dataset, we used immunoprecipitations of Ago2-associated mRNAs followed by micro-array analysis. The results demonstrate that Imp8 is required for recruiting Ago protein complexes to a large set of Ago2-associated target mRNAs allowing for efficient and specific gene silencing. Therefore, we provide evidence that Imp8 is required for cytoplasmic miRNA-guided gene silencing.
Publication Title
Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs.
Sample Metadata Fields
No sample metadata fields
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