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GSE46287
Mus musculus
12 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Tmprss6 is the master inhibitor of hepcidin and its inactivation causes iron refractory iron deficiency anemia both in human and in mice. Mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficienct-high hepcidin Tmprss6 null mice. We investigated the transcriptional response associated with chronic hepcidin overexpression by comparing whole genome transcription profiling of the liver of Tmprss6 KO mice and IDA animals, irrespective of iron deficiency.
Publication Title
A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
NextSeq 500
Description
In Multiple Sclerosis, the pathological interaction of autoreactive helper T (TH) cells with mononuclear phagocytes in the central nervous system (CNS) drives initiation and maintenance of chronic neuroinflammation. Herein, we found that intrathecal transplantation of neural stem cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived dendritic cells (moDCs) in the CNS leading to improved clinical outcome. NPCs treatment reduced in the CNS IL-23, IL-1 and TNF-a, cytokines required for terminal differentiation of TH cells and accordingly GM-CSF-producing pathogenic TH cells. In vivo and in vitro transcriptome analyses disclosed that NPC secreted factors induce an inhibition of DC differentiation and maturation, favoring a fate switch towards an anti-inflammatory phenotype. We identified TGF-ß2 as the crucial mediator of NPC immunomodulation: TGFß2 knockout NPCs transplanted in EAE are ineffective in impairing moDC accumulation within the CNS and fail to drive clinical improvement. This study provides evidence that intrathecally injected NPCs interfere with CNS-compartmentalized inflammation of the effector phase of EAE, reprogramming, through the secretion of TGF-ß2, inflammatory monocyte-derived DCs towards anti-inflammatory myeloid cells. Overall design: mRNA profiles of monocyte derived-dendritic cells (moDCs) isolated by FACS sorting at 7 days post-treatment from the CNS (hindbrain and spinal cord) of quadruplicate pool of 4–7 MOG35-55-immunized C57Bl/6 mice either intrathecally injected with PBS or 1 million neural precursor cells (NPCs) at the peak of the disease (2-4 days after clinical onset).
Publication Title
Neural precursor cell-secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene Expression Array (primeview), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The innate inflammatory response must be tightly regulated to ensure effective immune protection while avoiding inflammation-related pathologies. The transcription factor NF-kB is a critical mediator of the inflammatory response, and its dysregulation has been associated with immune related malignancies. We herein show that miR-155, miR-146a and NF-kB form a regulatory network that tunes the macrophage inflammatory response in mice. We show that elevated miR-155 expression potentiates NF-kB activity in miR-146a deficient mice, thus leading to an overactive acute inflammatory response and chronic inflammation. Enforced miR-155 expression overrides miR-146a-mediated repression of NF-kB activation, thus emphasizing that miR-155 plays a dominant, downstream role in promoting inflammation. We further show that miR-155 deficient macrophages exhibit a suboptimal inflammatory response when exposed to low levels of inflammatory stimuli. Importantly, we demonstrate a temporal asymmetry between miR-155 and miR-146a expression during macrophage activation, which forms a combined positive and negative feedback network on NF-kB activity. This miRNA based regulatory network enables a robust and time-limited inflammatory response essential for functional immunity. Overall design: RNA-seq of wild-type and microRNA-146/155 knock-out bone marrow derived macrophages after LPS stimulation
Publication Title
An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the pre-pro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in increased B cell output under non-homeostatic conditions. We find that miR-212/132 regulates B lymphopoiesis by targeting the transcription factor SOX4. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from over-expression of miR-132 alone. In addition, we show that the expression of miR-132 in cells that are prone to spontaneous B cell cancers can have a protective effect on cancer development. We have thus uncovered a novel regulator of B cell lineage specification that may potential applications in B cell cancer therapy Overall design: RNA-seq of wild-type and microRNA-212/132 knock-out B-cells after IgM stimulation
Publication Title
The microRNA-212/132 cluster regulates B cell development by targeting Sox4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Quantitative Analysis of cortical transcriptomes through Next Generation Sequencing (RNA-Seq) from wild-type mice, wild-type mice treated with IL1b (200 ng/mouse, 14h), IL-1R8-/- mice and IL-1R8-/- mice treated with IL1b antagonist Anakinra (25 mg/kg per day for 3 consecutive days, i.p. administration). mRNA profiles of cortical tissue from adult wild-type mice, wild-type mice treated with IL1b (200 ng/kg, 14h), IL-1R8-/- mice (Garlanda et al., 2004), and IL-1R8-/- mice treated with Anakinra (25 mg/kg per day for 3 consecutive days, i.p. administration) were generated by next-generation sequencing (RNA-seq) using Illumina HiSeq 2500 apparatus in paired-end configuration (2x125bp). Each condition was assessed in triplicate (12 mRNA-seq libraries) and, to reduce biological variability, each mRNA library was generated from pooled total RNA isolated from cortical tissue of 3 individual mice. In total, 9 mice per condition were used. Libraries were stranded and multiplexed. To increase sequencing depth, libraries were sequenced in two different lanes. All the libraries were loaded in each of the two lanes. Quality control of the raw data was performed with FastQC (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). Libraries were trimmed for adapter removal using Trimmomatic (Bolger et al., 2014) and mapped to reference genome (Ensembl GRCm38) using TopHat2 (Kim et al., 2013) and Bowtie2 (Langmead et al., 2009). Library sizes of primary mapped reads were between 70 and 96 million reads. Samtools was used to manipulate BAM files (Li et al., 2009). For calling of differentially expressed genes (DEG), mapped reads were counted with HTSeq v0.6.1 (Anders et al., 2014) and count tables were analysed using DeSeq2 v1.10.1 R-package (Love et al., 2014) with a design of one factor with four levels (“wild-type”, “wild-type + IL1?”, “IL-1R8-/-”, “IL-1R8-/- + Anakinra"), and differences between groups were tested using contrasts for wild-type + IL1b versus wild-type; IL-1R8-/- versus wild-type; IL-1R8-/- + Kineret versus wild-type. For consideration of differentially regulated genes between conditions, we used adjusted p-value < 0.1 or adjusted p-value < 0.05 as indicated in the manuscript. Overall design: mRNA profiles in adult mouse cerebral cortex of wild type (WT), WT mice treated with IL1b (200 ng/kg, 14h), IL-1R8-/- mice, and IL-1R8-/- mice treated with IL1b antagonist Anakinra (25 mg/kg per day for 3 consecutive days, i.p. administration) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Each sample was prepared by pooling cortical tissue from 3 idenpendent mice.
Publication Title
Lack of IL-1R8 in neurons causes hyperactivation of IL-1 receptor pathway and induces MECP2-dependent synaptic defects.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
WT and Ikbke-/- EF cells were stimulated with recombinant interferon beta for 6 hours. Cells lacking IKKe kinase show a defect in a subset of interferon stimulated gene transcription
Publication Title
Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Pmr1 is a cis-Golgi Mn/Ca transporter with a key role in protein glycosylation and manganese detoxification.
Publication Title
Manganese redistribution by calcium-stimulated vesicle trafficking bypasses the need for P-type ATPase function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- NextSeq 500
Description
Purpose: To ensure that ABX464 acted specifically on HIV splicing and did not significantly or globally affect the splicing events of human genes, we used an assembly approach of HIV (YU2 strain) putative transcripts and human long non-coding sequences from paired-reads (2x75bp) captured on a NimbleGen SeqCap® EZ Developer Library (Roche/NimbleGen). Methods: Cells were infected with 80 ng of p24/106 cells of the YU-2 strain for 4 to 6 hours and then rinsed with PBS before medium renewal, followed by high-throughput RNAseq from custom SeqCap EZ capture libraries. Each raw dataset of the samples contained between 5 and 30 million paired-end reads (75 bp), with an average of approximately 12 million raw reads per sample. Results: The raw reads were then cleaned and assembled per library to generate contigs, giving an average of 930 contigs per sample for further analyses. Conclusions: Our results show that high-throughput analyses coupled with bioinformatics-specific tools offers a comprehensive and more accurate view of mRNA splicing within a cell. Overall design: We used buffy coats from HIV-negative individuals were obtained from the local blood donation center, then human peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll (Histopaque, Sigma) gradient centrifugation. Cells were infected with 80 ng of p24/106 cells of the YU-2 strain for 4 to 6 hours and then rinsed with PBS before medium renewal.
Publication Title
Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CD8 positive dendritic cell line , stimulated with or without TLR3 ligand polyI:C
Publication Title
TLR3-Mediated CD8+ Dendritic Cell Activation Is Coupled with Establishment of a Cell-Intrinsic Antiviral State.
Sample Metadata Fields
Specimen part, Treatment
View Samples