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GSE44266
Homo sapiens
7 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders.
Publication Title
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Illumina HiSeq 2000
Description
Polycomb repressive complex 2 (PRC2) catalyzes histone H3K27me3, which characterizes many silenced genes including those on the inactive X-chromosome. Here we interrogate the role of core PRC2 protein EED in X-linked gene silencing by assessing allele-specific X-linked gene expression in WT and Eed-/- hybrid mouse trophoblast stem cells (TSCs) harboring a 129/S1-derived maternal X-chromosome and a JF1/Ms-derived paternal X-chromosome. This study generates mRNA-seq data for WT and Eed-/- TSCs, which undergo imprinted inactivation of the paternal X-chromosome. RNA-seq data was mapped allele-specifically to in silico strain-specific maternal and paternal reference genomes, generated based on known single nucleotide polymorphisms. We find that EED loss abrogates H3K27me3 and expression of Xist lncRNA, which is required for X-inactivation, however, despite the absence of H3K27me3 and Xist, only a subset of PRC2 target genes are derepressed in Eed-/- TSCs. Overall design: RNA-seq profiles of four WT (Eed +/+ and Eed fl/fl) and three EED null (Eed -/-) female TS cell lines were generated through strand-specific 100 bp paired-end sequencing on the Illumina HiSeq2000
Publication Title
PRC2 represses transcribed genes on the imprinted inactive X chromosome in mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The objective of the experiment is to determine the genes differentially expressed in the liver of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Publication Title
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The objective of the experiment is to determine the genes differentially expressed in the adrenal gland of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Publication Title
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
TBX5 is hypomethylated in Rheumatoid Arthritis synovial fibroblasts (RASF). Hypomethylation increased the TBX5 expression in RASF.
Publication Title
Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 351 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 128 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 120 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Subject, Time
View Samples