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GSE44265
Homo sapiens
11 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent.
Publication Title
HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- 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- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Aberrant splicing is a hallmark of leukemias with mutations in splicing factor (SF)-encoding genes. Here we investigated its prevalence in pediatric B-cell acute lymphoblastic leukemias (B-ALL), where SFs are not mutated. By comparing them to normal pro-B cells, we found thousands of aberrant local splice variations (LSVs) per sample, with 279 LSVs in 241 genes present in every comparison. These genes were enriched in RNA processing pathways and encoded ~100 SFs, e.g. hnRNPA1. hnRNPA1 3'UTR was most pervasively misspliced, yielding the transcript subject to nonsense-mediated decay. Thus, we knocked it down in B-lymphoblastoid cells, identified 213 hnRNPA1-dependent splicing events, and defined the hnRNPA1 splicing signature in pediatric leukemias. One of its elements was DICER1, a known tumor suppressor gene; its LSVs involved the 5' UTR, suggestive of splicing as a mechanism of translational deregulation. Additionally, we searched for LSVs in other leukemia and lymphoma drivers and discovered 81 LSVs in 41 genes. 77 LSVs were confirmed using two large independent B-ALL RNA-seq datasets. In fact, the twenty most common B-ALL drivers showed higher prevalence of aberrant splicing than of somatic mutations. Thus, post-transcriptional deregulation of SF can drive widespread changes in B-ALL splicing and likely contribute to disease pathogenesis. Overall design: We profiled hnRNPA1 Ctrl and hnRNPA1 knockdown with 2 replicates each.
Publication Title
Aberrant splicing in B-cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency; we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population
Publication Title
Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cross-presentation of cell-associated antigens is carried out by classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs), but whether a similar or distinct program exists for this process is unknown. In examining this issue, we discovered that only Ly-6ChiTremL4 monocytes, but not Ly-6ChiTremL4+ monocytes, can differentiate into Zbtb46+ Mo-DCs in response to GM-CSF and IL-4. However, Ly-6ChiTremL4+ monocytes were committed to Nur77-dependent development of Ly-6CloTremL4+ monocytes. Further, differentiation of monocytes with GM-CSF required addition of IL-4 to generate Zbtb46+ Mo-DCs that cross-presented as efficiently as CD24+ cDCs, which was accompanied by increased Batf3 and Irf4 expression. Unlike cDCs, Mo-DCs required only IRF4, and not Batf3, for cross-presentation. Further, Irf4/ monocytes failed to develop into Zbtb46+ Mo-DCs, and instead developed into macrophages. Thus, cDCs and Mo-DCs use distinct transcriptional programs for cross-presentation that may drive different antigen-processing pathways. These differences may influence development of therapeutic DC vaccines based on Mo-DCs.
Publication Title
Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cross-presentation of cell-associated antigens is carried out by classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs), but whether a similar or distinct program exists for this process is unknown. In examining this issue, we discovered that only Ly-6ChiTremL4 monocytes, but not Ly-6ChiTremL4+ monocytes, can differentiate into Zbtb46+ Mo-DCs in response to GM-CSF and IL-4. However, Ly-6ChiTremL4+ monocytes were committed to Nur77-dependent development of Ly-6CloTremL4+ monocytes. Further, differentiation of monocytes with GM-CSF required addition of IL-4 to generate Zbtb46+ Mo-DCs that cross-presented as efficiently as CD24+ cDCs, which was accompanied by increased Batf3 and Irf4 expression. Unlike cDCs, Mo-DCs required only IRF4, and not Batf3, for cross-presentation. Further, Irf4/ monocytes failed to develop into Zbtb46+ Mo-DCs, and instead developed into macrophages. Thus, cDCs and Mo-DCs use distinct transcriptional programs for cross-presentation that may drive different antigen-processing pathways. These differences may influence development of therapeutic DC vaccines based on Mo-DCs.
Publication Title
Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cross-presentation of cell-associated antigens is carried out by classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs), but whether a similar or distinct program exists for this process is unknown. In examining this issue, we discovered that only Ly-6ChiTremL4 monocytes, but not Ly-6ChiTremL4+ monocytes, can differentiate into Zbtb46+ Mo-DCs in response to GM-CSF and IL-4. However, Ly-6ChiTremL4+ monocytes were committed to Nur77-dependent development of Ly-6CloTremL4+ monocytes. Further, differentiation of monocytes with GM-CSF required addition of IL-4 to generate Zbtb46+ Mo-DCs that cross-presented as efficiently as CD24+ cDCs, which was accompanied by increased Batf3 and Irf4 expression. Unlike cDCs, Mo-DCs required only IRF4, and not Batf3, for cross-presentation. Further, Irf4/ monocytes failed to develop into Zbtb46+ Mo-DCs, and instead developed into macrophages. Thus, cDCs and Mo-DCs use distinct transcriptional programs for cross-presentation that may drive different antigen-processing pathways. These differences may influence development of therapeutic DC vaccines based on Mo-DCs.
Publication Title
Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altered compensatory cytokine signaling underlies the discrepancy between <i>Flt3<sup>-/-</sup></i> and <i>Flt3l<sup>-/-</sup></i> mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The goal of this study was to determine whether there are any gene expression changes in cDC1s and cDC2s from WT, Flt3 KO, or Flt3L KO mice. Specifically whether developing in the absence of Flt3 signaling had any effects on the gene expression of the cDCs
Publication Title
Altered compensatory cytokine signaling underlies the discrepancy between <i>Flt3<sup>-/-</sup></i> and <i>Flt3l<sup>-/-</sup></i> mice.
Sample Metadata Fields
Specimen part
View Samples