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SRP048971
Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2000
Description
Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with risk of autoimmune and immune-related disorders (AID), our understanding of the diseases mechanisms is limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). LncRNAs are known to show more cell-type specificity than protein-coding genes. Methods: In this study, we aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AID which have been well-defined by Immunochip analysis, by transcriptome analysis across seven peripheral blood leukocyte populations (granulocytes, monocytes, NK cells, B-cells, memory-T cells, naive CD4+ and naive CD8+ T-cells) and four cord blood derived T-helper cell populations (precursor, primary, polarized (Th1, Th2) T-helper cells). Results: We show that lncRNAs mapping to loci shared between AIDs are significantly enriched in immune cell types when compared to lncRNAs from the whole genome (a<0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five cell types enriched (a<0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis; memory-T and CD8+ T-cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis). Furthermore we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. Conclusions: The observed enrichment of lncRNA transcripts in AID loci implies an important role for lncRNAs in AID etiology and suggests that lncRNA genes should be studied in more detail to correctly interpret GWAS findings. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways. Overall design: 7 immune cell types
Publication Title
Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
Gene expression profiles 6 hours post-influenza A virus infection in human monocytes at multiplicities of infection of 10 versus uninfected monocytes
Publication Title
Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Accurate and reproducible quantitation of target genes depends on correct normalization. Historically, genes with variable tissue transcription e.g. GAPDH, have been used as normalization factors which is problematic, particularly in clinical samples which often are derived from different tissue sources. Using a large-scale gene database (GeneChip (Affymetrix U133A) dataset of 36 gastrointestinal tumors and normal tissues), we identified 8 candidate reference genes that were highly expressed with low variability and established expression levels by real-time RT-PCR in an independent set of GI tissue samples (n=42).
Publication Title
GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real-time PCR.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Integration of multiple signals shapes cell adaptation to their microenvironment through synergistic and antagonistic interactions. The combinatorial complexity governing signal integration for multiple cellular output responses has not been resolved. For outputs measured in the conditions 0 (control), signals X, Y, X+Y, combinatorial analysis revealed 82 possible interaction profiles, which we biologically assimilated to 5 positive, and 5 negative interaction modes. To experimentally validate their use in living cells, we designed an original computational workflow, and applied it to transcriptomics data of innate immune cells integrating physiopathological signal combinations. Up to 9 of the 10 defined modes coexisted in context-dependent proportions. Each integration mode was enriched in specific molecular pathways, suggesting a coupling between genes involved in particular functions, and the corresponding mode of integration. We propose that multimodality and functional coupling are general principles underlying the systems level integration of physiopathological and pharmacological stimuli by mammalian cells.
Publication Title
Combinatorial code governing cellular responses to complex stimuli.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was 'cell movement' including E-selectin, which was coordinately regulated with IL-1beta. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1beta, which together with IFN-gamma, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.
Publication Title
Integrated pathways for neutrophil recruitment and inflammation in leprosy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparison of Mpl-/- mouse LSK cells, either treated with control (GFP) or Mpl lentivirus. Lineage negative bone marrow cells were isolated and transduced and transplanted into Mpl-/- recipient mice. After transplantation and follow up mice were sacrificed and LSK (lineage negative, Sca-1 positive, cKit positive) cells were isolated by FACS. RNA was isolated using RNeasy Micro Kit (Qiagen GmbH, Hilden, Germany) and RNA was amplified for microarray hybridization using the Nugen Ovation system (Nugen Technologies, AC Bemmel, Netherlands). The resulting material was hybridized to Affymetrix Mouse 430 2.0 arrays. RMA normalization and summarization was performed in R 2.10 using Bioconductor packages. The aim was to show the normalization of Mpl associated gene expression.
Publication Title
Lentiviral gene transfer regenerates hematopoietic stem cells in a mouse model for Mpl-deficient aplastic anemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 68 Downloadable Samples
- Illumina HiSeq 2000
Description
Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs) to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways have been shown to contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways responsible for the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, only two PRR pathways – the Toll-like receptor (TLR) and Stimulator of Interferon Gene (STING) pathways - were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated an inflammatory program, STING signaling activated an antiviral/type I interferon response, and both pathways contributed to a program linking innate and adaptive immunity. Only a small number of genes were induced in the absence of TLR or STING signaling, and these genes possessed a strong hypoxia signature. STING pathway activation required live S. aureus and was largely dependent on the DNA sensor cyclic guanosine-adenosine synthase (cGAS) recognition of S. aureus DNA. Interestingly, using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus, with TLR signaling being required for protective interleukin (IL)-1? and neutrophil recruitment and STING signaling having an opposite effect. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered byS. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus. Overall design: Files are labeled according to the figures in which they were used. Note, that many data files were used in multiple figures or figure panels. Files are labeled by genotype of macrophages (WT=wildtype; KO= StingGt/Gt; DKO=MyD88-/-TRIF-/-) and whether the macrophages were treated with live (Live) or heat killed (HK) or uninfected (zero hour). Labeling of time points is in the order of "minutes_replicate #." For example, "WT_HK_30_2" indicates that this is wild type mouse macrophages stimulated with heat killed bacteria at the 30-minute time point and is replicate number 2. Reads were converted into RPKM, and the RPKM for all replicates listed for a given time point were averaged to obtain the average RPKM that was used for figures and analyses. For samples listed as contributing to either figure 3 or supplemental figure 2, the replicates that do NOT end in either KO_analysis nor DKO analysis were used to determine induced genes in wild type macrophages. In contrast, the replicates that end in KO_analysis or DKO_analysis were used to determine dependence on either STING signaling or MyD88/TRIF signaling, respectively. If a replicate was used in the STING or MyD88/TRIF dependence analysis for both live and heat-killed S. aureus, "live_and_hk" was added after the dependence analysis it contributed to. Some 0h samples were used in both live and heat-killed analyses.
Publication Title
Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mouse LT-HSC were sorted and cultured in mScf, mTpo, mFlt3L, hIGFBP2 and Angptl5 for 2 days. These expression values were related to insertions of gamma-retroviral, lentiviral or alpharetroviral vectors carrying GFP which were retrieved after serial murine BM transplantation. The relation between gene expression in the cells responsible for long-term hematopoiesis and location of vector integration was investigated.
Publication Title
Alpharetroviral self-inactivating vectors: long-term transgene expression in murine hematopoietic cells and low genotoxicity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
human blood monocytes were isolated, activated and harvested at several timepoints
Publication Title
NOD2 triggers an interleukin-32-dependent human dendritic cell program in leprosy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome profiles for innate and adaptive immune stimuli important for host response against mycobacteria. Human monocyte-derived macrophages were stimulated with TLR2/1 ligand and interferon-g, stimuli present during innate and adaptive immune responses, respectively. Overall design: Human monocyte-dervided macrophages from five healthy donors were stimulated with TLR2/1L, IFN-g, or media control for 2, 6, and 24 hours. RNA-sequencing was performed on a total of 45 samples.
Publication Title
S100A12 Is Part of the Antimicrobial Network against Mycobacterium leprae in Human Macrophages.
Sample Metadata Fields
Specimen part, Subject
View Samples