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GSE114718
Mus musculus
102 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Malaria is a disease with diverse symptoms depending on host immune status and pathogenicity of Plasmodium parasites. The continuous parasite growth within a host suggests mechanisms of immune evasion and/or inhibition. To identify pathways commonly inhibited by malaria infection, we infected C67BL/6 mice with four Plasmodium yoelii strains causing different disease phenotypes and 24 progeny of a genetic cross. mRNAs from mouse spleens day 1 and/or day 4 post infection (p.i.) were hybridized to a mouse microarray to identify activated or inhibited pathways, upstream regulators, and linkages to parasite genetic loci. Strong interferon responses were observed after infection with N67 strain, whereas initial inhibition and later activation of hematopoiesis pathways were found after infection with 17XNL parasite. Inhibition of pathways such as Th1 activation, dendritic cell (DC) maturation, and NFAT immune regulation were observed in mice infected with all the parasite strains day 4 p.i., suggesting universally inhibited immune pathways. Treatment of infected mice with antibodies against T cell receptors OX40 or CD28 to activate malaria-inhibited pathways enhanced host survival. Controlled activation of these pathways may provide important strategies for better disease management and for developing an effective vaccine.
Publication Title
Detection of host pathways universally inhibited after Plasmodium yoelii infection for immune intervention.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Geminin is a small nucleoprotein that neuralizes ectoderm in the Xenopus embryo. Geminin promotes neural fate acquisition of mouse embryonic stem cells: Geminin knockdown during neural fate acquisition decreased expression of neural precursor cell markers (Pax6, Sox1), while increasing expression of Pitx2, Lefty1 and Cited2, genes involved in formation of the mouse node. Here we differentiated mouse embryonic stem cells into embryoid bodies to study Geminin's ability to repress primitive streak mesendoderm fate acquisition. We used microarrays to define the sets of genes that are regulated by Geminin during cell fate acquisition in embryoid bodies, using Dox-inducible Geminin knockdown or overexpression mouse embryonic stem cell lines.
Publication Title
Geminin restrains mesendodermal fate acquisition of embryonic stem cells and is associated with antagonism of Wnt signaling and enhanced polycomb-mediated repression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Formation of the complex vertebrate nervous system begins when pluripotent cells of the early embryo are directed to acquire a neural fate. Although cell intrinsic controls play an important role in this process, the molecular nature of this regulation is not well defined. Here we assessed the role for Geminin, a nuclear protein expressed in embryonic cells, in neural fate acquisition from mouse embryonic stem (ES) cells. While Geminin knockdown does not affect the ability of ES cells to maintain or exit pluripotency, we found that it significantly impairs their ability to acquire a neural fate. Conversely, Geminin overexpression promotes neural gene expression, even in the presence of growth factor signaling that antagonizes neural transcriptional responses. These data demonstrate that Geminins activity contributes to mammalian neural cell fate acquisition. We investigated the mechanistic basis of this phenomenon and found that Geminin maintains a hyperacetylated and open chromatin conformation at neural genes. Interestingly, recombinant Geminin protein also rapidly alters chromatin acetylation and accessibility even when Geminin is combined with nuclear extract and chromatin in vitro. These findings define a novel activity for Geminin in regulation of chromatin structure. Together, these data support a role for Geminin as a cell intrinsic regulator of neural fate acquisition that promotes expression of neural genes by regulating chromatin accessibility and histone acetylation.
Publication Title
Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Expression profile of human donor lungs that have developed primary graft dysfunction (PGD) after lung transplantation and those that have not.
Publication Title
Expression profiling of human donor lungs to understand primary graft dysfunction after lung transplantation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Lim1 gene has essential functions during several stages of kidney development. In particular, a tissue specific knockout in the early metanephric mesenchyme results in the formation of the earliest nephron precursor, the renal vesicle, but failure of this structure to progress to the next stage, the comma shaped body. To better understand the molecular nature of this developmental arrest we used a laser capture microdissection-microarray strategy to examine the perturbed gene expression pattern of the mutant renal vesicles. Among the genes found differently expressed were Chrdl2, an inhibitor of BMP signaling, the pro-apoptotic factor Bmf, as well as myob5, an atypical myosin which modulates chemokine and transferring signaling, and pdgfr1, which is important in epithelial folding. Of particular interest, the microarray data indicated that the Dkk1 gene, which encodes an inhibitor of Wnt signaling, was downregulated nine fold in mutants. This was confirmed by in situ hybridizations. It is interesting to note that Lim1 and Dkk1 mutant mice have striking similarities in phenotype. These results suggest that the Dkk1 gene might be a key downstream effector of Lim1 function.
Publication Title
Laser capture-microarray analysis of Lim1 mutant kidney development.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
These investigations studied the fundamentals of how plants perceive gravity and develop in microgravity. It informs how gene regulation is altered by spaceflight conditions.
Publication Title
Comparative transcriptomics indicate changes in cell wall organization and stress response in seedlings during spaceflight.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within red blood cells (RBCs), thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi gene knockdown and knockout mice, we demonstrated that a strong IFN-I response triggered by RNA Polymerase III and melanoma differentiation-associated protein 5 (MDA5), not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine (PS) on infected RBC (iRBC) might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis.
Publication Title
Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Complete (whole) embryonic kidneys were dissected from wild type and Hoxa11, Hoxd11 compound null embryons throughout development. Targets from two biological replicates of each were generated and the expression profiles were determined using Affymetrix MOE430A and MOE430B arrays. Comparisons between normal and mutant and comparisons of development samples identified global patterns of gene regulation in kidney development
Publication Title
Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
E11.5 metanephric mesenchyme and ureteric bud were dissected from the E11.5 kidney rudiment using fine manual microdissection (ureteric bud only) or both fine manual microdissection and laser capture microdissection (metanephric mesenchyme) to define the gene expression profiles of these structures. Additionally, HoxA11, HoxD11 compound null E11.5 metanephric mesenchyme was obtained through laser capture microdissection allowing analysis of possible Hox targets in kidney development. Targets from multiple biological replicates of each were generated and the expression profiles were determined using Affymetrix MOE430_v2 arrays.
Publication Title
Comprehensive microarray analysis of Hoxa11/Hoxd11 mutant kidney development.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 15 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants aquire nitrogen from the soil, most commonly in the form of either nitrate or ammonium. Unlike ammonium, nitrate must be reduced (with NADH and ferredoxin as electron donors) prior to assimilation. Thus, nitrate nutrition imposes a substantially greater energetic cost than ammonium nutrition. Our goal was to compare the transcriptomes of nitrate-supplied and ammonium-supplied plants, with a particular interest in characterizing the differences in redox metabolism elicited by different forms of inorganic nitrogen.
Publication Title
Distinct signalling pathways and transcriptome response signatures differentiate ammonium- and nitrate-supplied plants.
Sample Metadata Fields
Specimen part
View Samples