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GSE12787
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 2496 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, while mf exposure did not induce apoptosis in macrophages. Interestingly, 48 h exposure of DC to mf induced mRNA expression of the pro-apoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. Mf also induced gene expression of BH3-interacting domain death agonist (Bid) and protein expression of cytochrome c in DC; mf-induced cleavage of Bid could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion.
Publication Title
Induction of TRAIL- and TNF-alpha-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi.
Sample Metadata Fields
Sex, Treatment, Race
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
Goal: To examine the effects of human resistin during helminth infection. Methodology: To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene along with its entire regulatory region (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis, whole lung RNA was sequenced in hRetnTg+ mice, control hRetnTg- and naïve mice. Conclusion: In hRetnTg+ mice, many genes involved in inflammation and the immune system, specifically toll-like receptor signaling and chemokines, are significantly upregulated, suggesting that human resistin promotes TLR signaling and inflammation during helminth infection. Overall design: Examination of whole lung mRNA from Nippostrongylus brasiliensis-infected lungs at day 7 in mice expressing human resistin
Publication Title
Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 232 Downloadable Samples
- IlluminaHiSeq2000
Description
Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but not Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies transcriptomic analyses to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually. Overall design: 108 samples; paired pre- and post-challenge for 54 individuals 198 samples; paired pre- and post-challenge for 99 individuals
Publication Title
Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Background: Transposable elements are known to influence the regulation of some genes. We aimed to determine which genes show altered gene expression when transposable elements are epigenetically activated.
Publication Title
Genome-wide identification of genes regulated in trans by transposable element small interfering RNAs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Ets1-/- mice have an increase in B cell differentiation to plasma cells and increased serum immunoglobulin levels. The genes in B cells that are transcriptionally regulated by Ets1 and help regulate B cell differentiation are largely unknown. Here, we identify Ets1-regulated target genes in B cells using ChIP-seq and RNA-seq analysis. We found that Ets1 targets genes associated with immune response, mature B cell differentiation and regulation of B cell activation. Overall design: Quiescent follicular B cells were sorted from the spleens of wild-type and Ets1-/- mice using the following markers B220+ CD23-high CD21-low CD80-negative IgA-negative IgE-negative IgG1-negative IgG2a-negative IgG2b-negative IgG3-negative. Total RNA was prepared from sorted cells and subjected to RNA-sequencing.
Publication Title
Genome-Wide Identification of Target Genes for the Key B Cell Transcription Factor <i>Ets1</i>.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Overall study: Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells.
Publication Title
Autocrine platelet-derived growth factor-dependent gene expression in glioblastoma cells is mediated largely by activation of the transcription factor sterol regulatory element binding protein and is associated with altered genotype and patient survival in human brain tumors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
LYVE-1-positive macrophages were observed to be closely spatially associated with the developing lymphatic vasculature. The role of this population of macrophages in the embryo is uncharacterised.
Publication Title
Macrophages define dermal lymphatic vessel calibre during development by regulating lymphatic endothelial cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The Ets family transcription factor PU.1 is essential for the development and maintenance of several hematopoietic lineages. In the thymus, PU.1 is expressed only in the early ETP/DN1, DN2a and DN2b stages of development. While PU.1 deletion in multipotent precursors leads to a complete block in T-cell development its function in the intrathymic stages in which it is expressed remains undetermined. The goal of this expression profiling study was to determine if PU.1 regulates the expression of T-lineage genes during the early stages of development. To do this, we generated the PU.1-Eng construct which expresses a fusion protein containing the DNA binding ETS domain of PU.1 (aas 159-260) fused to the obligate repressor domain (aas 1-298) of the Drosophila engrailed protein. The PU.1-ETS construct only expresses the ETS domain of PU.1 (aas 159-260) and serves as a control. Fetal liver precursors were isolated from e14.5 embryos and co-cultured with OP9-DL1 cells in the presence of IL-7 and Flt3L (5 ng/ml each) for 4 days to obtain FLDN1, DN2a and DN2b cells. These were infected with vector only, PU.1-ETS and the PU.1-Eng constructs and DN2 cells were sorted after 20 hours of infection. Total RNA was isolated from these cells and polyA+ fraction was used to prepare libraries for high throughput sequencing. Libraries prepared from 2 independent sets of samples were subjected to non-strand specific single-end sequencing. Overall design: Two sets of samples generated from fetal liver precursor derived DN2 cells expressing PU.1-ETS and PU.1-Eng constructs were used for expression profiling. The LZRS retroviral vector, without any insert, was used to generate the vector control dataset.
Publication Title
Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Pre-mRNA splicing is regulated through combinatorial activity of RNA motifs including splice sites and splicing regulatory elements (SREs). Here, we show that the activity of a major class of mammalian SREs is highly sensitive to the strength of the adjacent 5'' splice site (5''ss) sequence, and that this has important functional and evolutionary implications. Activity of G-run SREs was higher for intermediate strength 5''ss by ~4-fold relative to weak 5''ss, and by ~1.3-fold relative to strong 5''ss. The dependence on 5''ss strength was supported both by comparative genomics and by microarray and Illumina mRNA-Seq analyses of splicing changes following RNAi against the splicing factor heterogeneous nuclear ribonucleoprotein (hnRNP) H, which binds G-runs. This dependence implies that the responsiveness of exons to changes in hnRNP H levels is a bivariate function of both SRE abundance and 5''ss strength; this relationship may hold also for other splicing factors. This pattern of activity enables G-runs and hnRNP H to buffer the effects of 5''ss mutations, augmenting both the frequency of 5''ss polymorphism and the evolution of new splicing patterns. Overall design: Examine mRNA expression in 293T cells following hnRNP H or control siRNA knockdown
Publication Title
Splice site strength-dependent activity and genetic buffering by poly-G runs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 3000
Description
Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 co-chaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells (ASCs). By analyzing Mzb1 -/- Prdm1 +/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of ASCs in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1 -/- plasmablasts show a reduced activation of b1 integrin, which contributes to the impaired plasmablast differentiation and migration of ASCs to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation. Overall design: Splenic B cells were purified from Mzb1 +/+ Prdm1 +/gfp and Mzb1 -/- Prdm1 +/gfp mice using anti-B220 magnetic beads and cultured in the presence of 25ug/ml LPS. After 4 days, undifferentiated CD138 - Blimp - B cell blasts (Activated B Cells), CD138 - Blimp + (Pre-PB cells), and CD138 + Blimp + (PB cells) were isolated with FACSAria (Becton Dickinson) sort.
Publication Title
Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples