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SRP064515
Homo sapiens
198 Downloadable Samples
IlluminaHiSeq2500, IlluminaHiSeq2000
Description
Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. However, post-transcriptional mechanisms involved in mRNA processing have been poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Overall design: Transcriptomic profiles of 198 infected (Listeria and Salmonella) and non-infected samples at multiple time points.
Publication Title
Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- IlluminaHiSeq2500
Description
DNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells with a live pathogenic bacteria is associated with rapid changes in methylation levels at thousands of loci. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced changes in methylation rarely occur at promoter regions and instead localize to distal enhancer elements. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and the induction of enhancer RNAs, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response of immune cells to infection. Overall design: Transcriptional profiles (polyA+) of 6 non-infected and 6 MTB-infected dendritic cell samples.
Publication Title
Bacterial infection remodels the DNA methylation landscape of human dendritic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 4000
Description
Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5 year-old child with severe pulmonary influenza at 2 years. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not interferon-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-a2b. The transcriptome induced by IFN-a2b in the patient's cells is much narrower than that of control cells; however, induction of a subset of interferon-stimulated gene transcripts remains detectable. In vitro, the patient's cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus, and respiratory syncytial virus. These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV. Overall design: Total of 72 samples, 38 samples from primary fibroblasts and 34 samples from EBV-transformed B cells, were analyzed using paired-end RNA sequence data. Out of 38 samples from primary fibroblasts, 3 control samples are paired with no stimulation vs IFNa2b stimulation. Out of 34 samples from B-cells, 3 control samples are paired with no stimuliion vs IFNa2b stimulation. In addition to healthy control subjects, patients with AR complete STAT1 (STAT1 -/-) or STAT2 (STAT2 -/-) deficiency were analyzed for comparison.
Publication Title
Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Adenosine, prostaglandin E2, or increased intracellular cyclic AMP concentration each elicit potent anti-inflammatory events in human neutrophils by inhibiting functions such as phagocytosis, superoxide production, adhesion and cytokine release. However, the endogenous molecular pathways mediating these actions are poorly understood. In the present study, we examined their impact on the gene expression profile of stimulated neutrophils. We have identified a set of genes that may be part of important resolution pathways that interfere with cell activation. Identification of these pathways will improve understanding of the capacity of tissues to terminate inflammatory responses and contribute to the development of therapeutic strategies based on endogenous resolution
Publication Title
Impact of anti-inflammatory agents on the gene expression profile of stimulated human neutrophils: unraveling endogenous resolution pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 73 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
mRNA expression was assayed from bronchial epithelial cells collected via bronchoscopy and nasal epithelial cells collected by brushing the inferior turbinate from healthy current and never smoker volunteers in order to determine the relationship between smoking-related gene expression changes in bronchial and nasal epithelium within the same individual.
Publication Title
Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Smoking is the leading cause of lung cancer death, although only a small percentage of smokers develop the disease. Cigarette smoke exposure is known to cause a field of injury in cells throughout the respiratory tract, and while these airway epithelial cells are morphologically normal, they can undergo genetic alterations in response to cigarette smoke exposure.
Publication Title
Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Vitamin D is a secosteroid that has multiple regulatory roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer's disease, Parkinson's disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 induced expression of SKN-1 target genes, but not canonical targets of IRE-1/XBP-1. Vitamin D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented the toxicity caused by human ß-amyloid. Our observation that vitamin D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with a vitamin D deficiency. Overall design: The experimental design consisted of contrasting gene expression data derived from RNA extracted from pools of synchronized aged worms. L4 worms were placed on either vehicle (DMSO) or Vitamin D (100uM) for 44 hours prior to extraction. A pool of 50 worms was considered a single biological replicate. For the Vitamin D treated group, there were 6 independent biological replicates, and were compared with a group of untreated (vehicle) wild-type N2 animals, also using 6 biological replicates.
Publication Title
Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated analysis of global mRNA and protein expression data in HEK293 cells overexpressing PRL-1.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The multifunctional protein tyrosine phosphatase PRL-1 (Gene Symbol: PTP4A1) has been identified as an important oncogene with roles in promoting cell proliferation, survival, migration, invasion, and metastasis. However, little is currently known about the signaling pathways through which it mediates its effects.
Publication Title
Integrated analysis of global mRNA and protein expression data in HEK293 cells overexpressing PRL-1.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b), Affymetrix Mouse Expression 430A Array (moe430a)
Description
Effect of high fat diet feeding on gene expression
Publication Title
Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples