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GSE31747
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. Notably, some cellular interferon-inducible genes were upregulated six hours after exposure to virions and LPS, but not after exposure to VLPVP40-GP. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response.
Publication Title
Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Using high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology.
Publication Title
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Illumina Genome Analyzer II
Description
Using high throughput sequencing of Drosophila head RNA, a small set of miRNAs that undergo robust circadian oscillations in levels were discovered. We concentrated on a cluster of six miRNAs, mir-959-964, all of which peak at about ZT12 or lights-off. The data indicate that the cluster pri-miRNA is transcribed under bona fide circadian transcriptional control and that all 6 mature miRNAs have short half-lives, a requirement for oscillating. Manipulation of food intake dramatically affects the levels and timing of cluster miRNA transcription with no more than minor effects on the core circadian oscillator. This indicates that the central clock regulates feeding, which in turn regulates proper levels and cycling of the cluster miRNAs. Viable Gal4 knock-in as well as cluster knock-out and over-expression strains were used to localize cluster miRNA expression as well as explore their functions. The adult head fat body is a major site of expression, and feeding behavior, innate immunity, metabolism, and perhaps stress responses are under cluster miRNA regulation. The feeding behavior results indicate that there is a feedback circuit between feeding time and cluster miRNA function as well as a surprising role of post-transcriptional regulation in these behaviors and physiology. Overall design: Six samples of small RNA libraries (RNA size 19 to 29 nucleotides long) were prepared from Drosophila heads, each collected at one circadian time point during a light-dark cycle (ZT0, ZT4, ZT8, ZT12, ZT16, ZT20).
Publication Title
The oscillating miRNA 959-964 cluster impacts Drosophila feeding time and other circadian outputs.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these sub-haploinsufficient cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these sub-haploinsufficient cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases.
Publication Title
MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs.
Publication Title
Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients' HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors.
Publication Title
The hematopoietic stem cell in chronic phase CML is characterized by a transcriptional profile resembling normal myeloid progenitor cells and reflecting loss of quiescence.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
Affymetrix Mouse Expression 430B Array (moe430b), Affymetrix Mouse Expression 430A Array (moe430a)
Description
Gene expression profiling was performed on CNS tissue from neonatal mice carrying the T9H translocation and maternal or paternal duplication of proximal Chromosomes 7 and 15. Our analysis revealed the presence of two novel paternally expressed intergenic transcripts at the PWS/AS locus. The transcripts were termed Pec2 and Pec3 for paternally expressed in the CNS.Our analysis also revealed imprinting of Magel2, Mkrn3, Ndn,Ube3a and Usp29, as well as Pec2 and Pec3 in embryonic brain, 15.5 dpc, and provided a survery of biallelically expressed genes on proximal Chromosomes 7 and 15 in embryonic and neonatal CNS.
Publication Title
Novel paternally expressed intergenic transcripts at the mouse Prader-Willi/Angelman Syndrome locus.
Sample Metadata Fields
No sample metadata fields
View Samples