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.
Deregulation of microRNAs by HIV-1 Vpr protein leads to the development of neurocognitive disorders.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesPolycomb 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
PRC2 represses transcribed genes on the imprinted inactive X chromosome in mice.
Specimen part, Subject
View SamplesThe objective of the experiment is to determine the genes differentially expressed in the liver of the chromogranin A knockout mouse (Mahapatra et al., 2005).
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesThe 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).
Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification.
Sex, Specimen part
View SamplesTBX5 is hypomethylated in Rheumatoid Arthritis synovial fibroblasts (RASF). Hypomethylation increased the TBX5 expression in RASF.
Epigenome analysis reveals TBX5 as a novel transcription factor involved in the activation of rheumatoid arthritis synovial fibroblasts.
Specimen part
View SamplesThis study describes the transcriptome profiling of: 1) mouse ES cells in LIF/KSR medium; 2)EpiSCs in bFGF/serum-free (KSR) medium; 3) EpiSCs treated with MM401/LIF KSR at D3 and D6 (P2); 4) rES reverted form EpiSC by MM401/LIF KSR treatment at P6, P30 with or without MM401 . Overall design: RNA-Seq profiling on mouse pluripotent cells. Biological duplicates of each sample are labled as rep1/2.
MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency.
Specimen part, Subject
View SamplesHuman transcriptome array analysis of human cord blood mononuclear leokocytes from neonates exposed to histological chorioamnionitis and compared with healthy neonates
Histological Chorioamnionitis Induces Differential Gene Expression in Human Cord Blood Mononuclear Leukocytes from Term Neonates.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Specimen part, Subject, Time
View SamplesIL-4/GFP- enhanced transcript (4Get) reporter mice were infected with 200 PFU of Influenza A virus PR8 strain. At day 3 of infection, mediastinal lymph nodes were harvested and GFP+ cells sorted and separated by their ability to bind a CD1d-tetramer (Tet+ n=133 , Tet- n=109 ). Single-cell RNA-Seq was used to identify subpopulations of IL-4 producing cells. Single-cell transcriptomes were clustered using Seurat and differentially expressed genes within each cluster were used to resolve IL-4+ subpopulations and aid in defining their role in initiating B cell immunity during influenza infection. Overall design: Examine cells involved in accute viral response in the lymph node after influenza infection
Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.
Specimen part, Subject
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