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GSE36933
Homo sapiens
16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The apolipoprotein A-I (apoA-I) mimetic peptide 4F displays prominent anti-inflammatory properties, including the ability to reduce vascular macrophage content. Macrophages are a heterogenous group of cells, represented by two principal phenotypes, the classically activated M1 macrophage and an alternatively activated M2 phenotype. We recently reported that 4F favors the differentiation of human monocytes to an anti-inflammatory phenotype similar to that displayed by M2 macrophages. In the current study, microarray analysis of gene expression in monocyte-derived macrophages (MDMs) was carried out to identify inflammatory pathways modulated by 4F treatment. ApoA-I treatment of MDMs served as a control. Transcriptional profiling revealed that 4F and apoA-I modulated expression of 113 and 135 genes that regulate inflammatory responses, respectively. Cluster heat maps revealed that 4F and apoA-I induced similar changes in expression for 69 common genes. Modulation of other gene products, including STAT1 and PPARG, were unique for 4F treatment. Besides modulating inflammatory responses, 4F was found to alter gene expression in cell-to-cell signaling, cell growth/proliferation, lipid metabolism and cardiovascular system development. These data suggest that the protective effects of 4F in a number of disease states may be due to underlying changes in monocyte/macrophage gene expression.
Publication Title
Regulation of pattern recognition receptors by the apolipoprotein A-I mimetic peptide 4F.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B cell dysfunction due to unspecific B cell activation. How HIV-1 affects antigen-specific B cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T cell - B cell immune synapse. This interference reduced B cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
Publication Title
HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD138+ B220- plasma cells were sorted from bone marrow and B220+ CD23+ mature follicular B cells were sorted from the spleens. Plasma cells were sorted from C57BL/6 mice 7 days after boosting with antigen, with mice first primed with an i.p. injection of KLH/IFA followed by boost at day 21 with KLH/PBS i.p. Mature B cells were sorted from antigen-nave C57BL/6 mice.
Publication Title
Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We are submitting two small RNA libraries derived from ovarian tissue of mutant and heterozygous for the Kumo/Qin gene, required for the piRNA production in germline cells. In absence of Kumo/Qin, piRNA production is reduced and transposons are derepressed. Overall design: Analysis of piRNA production in Kumo/Qin mutants
Publication Title
The tudor domain protein kumo is required to assemble the nuage and to generate germline piRNAs in Drosophila.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Interferon-γ Inhibits Ebola Virus Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFN) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFN-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFN treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFN treatment inhibits genome replication. As IFN treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
Publication Title
Interferon-γ Inhibits Ebola Virus Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFN) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFN-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFN treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFN treatment inhibits genome replication. As IFN treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
Publication Title
Interferon-γ Inhibits Ebola Virus Infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Very little is known about splicing and its regulation in germ cells, particularly during meiosis. This paper describes the role of a male germ cell-specific protein, Tudor containing protein 6 (TDRD6), in assembly of the spliceosome in spermatocytes. We show that in spermatocytes, TDRD6 interacts with the key protein methyl transferase of the splicing pathway PRMT5. PRMT5 methylates arginines in substrate proteins. In a methylation dependent manner, TDRD6 also associates with spliceosomal core protein SmB in the absence of RNA, thus before an RNP-type spliceosome has been assembled. In Tdrd6-/- primary spermatocytes, PRMT5''s association with SmB and the arginine dimethylation of SmB are much reduced. Abrogation of arginine methylation impaired the assembly of spliceosomes and the presence of the spliceosomal RNA U5 is aberrantly increased. These deficiencies in spliceosome maturation correlated with decreased numbers of Cajal bodies and gems involved in later stages, i.e. nuclear snRNP maturation. To reveal functional consequences of these deficiencies, transcriptome analysis of primary spermatocytes showed high numbers of splicing defects such as aberrant usage of intron and exons as well as aberrant representation of splice junctions upon TDRD6 loss. This study reveals a novel function of TDRD6 in spliceosome maturation and mRNA splicing in spermatocytes. Overall design: Examination of splicing defects in isolated diplotene cells of 20dpp Tdrd6-/- vs. Tdrd6+/- testes pooled from at least 4 mice by deep sequencing in duplicate using Illumina® HiSeq 2500.
Publication Title
TDRD6 mediates early steps of spliceosome maturation in primary spermatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
How cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of WNT signaling upon knock-down (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFa as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the membrane localization, and thus function, of TGFa. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFa exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFa ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFa and GLI1 that enhances metastases. We suggest that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities. Overall design: CC14 and CC36, two primary colon cancer cells, were treated with control or shTMED9 expressing lentivirus. In addition, CC14 cells were also treated with shTMED3 expressing lentivirus. All the experiments were run in triplicates totaling 15 Samples.
Publication Title
The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
We applied previously established in silico whole-embryo body (WB)-subtraction-based approach to identify “lens-enriched” genes. These new RNA-seq datasets on embryonic stages E10.5, E12.5, E14.5 and E16.5 confirmed high expression of established cataract-linked genes and identified several new potential regulators in the lens. Finally, we present lens stage-specific UCSC Genome Brower annotation-tracks; these are publicly accessible through iSyTE (https://research.bioinformatics.udel.edu/iSyTE/) and enable a user-friendly visualization of lens gene expression/enrichment to help prioritize genes from high-throughput data from cataract cases. Overall design: RNA-sequencing datasets of microdissected embyonic eye lens samples from stages embryonic day E10.5, E12.5, E14.5 and E16.5 were generated. To estimate lens enriched genes we generated control “whole-embryo body (WB)” datasets. The lens enriched genes were used for enrichment level based clustering to identify gene clusters exhibiting distinct lens enrichment patterns across E10.5 to E16.5 developmental window. This new lens RNA-seq data and its accessibility through iSyTE 2.0 serves as a new integrative resource for prioritization of lens defects and/or cataract-linked candidate genes identified by other high-throughput analyses such as exome-seq and GWAS.
Publication Title
RNA sequencing-based transcriptomic profiles of embryonic lens development for cataract gene discovery.
Sample Metadata Fields
Cell line, Subject
View Samples