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Mus musculus
30 Downloadable Samples
Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Individual genetic variation affects gene expression and cell phenotype by acting within complex molecular circuits, but this relationship is still largely unknown. Here, we combine genomic and meso-scale profiling with novel computational methods to detect genetic variants that affect the responsiveness of gene expression to stimulus (responsiveness QTLs) and position them in circuit diagrams. We apply this approach to study individual variation in transcriptional responsiveness to three different pathogen components in the model response of primary bone marrow dendritic cells (DCs) from recombinant inbred mice strains. We show that reQTLs are common both in cis (affecting a single target gene) and in trans (pleiotropically affecting co-regulated gene modules) and are specific to some stimuli but not others. Leveraging the stimulus-specific activity of reQTLs and the differential responsiveness of their associated targets, we show how to position reQTLs within the context of known pathways in this regulatory circuit. For example, we find that a pleiotropic trans-acting genetic factor in chr1:129-165Mb affects the responsiveness of 35 anti-viral genes only during an anti-viral like stimulus. Using RNAi we uncover RGS16 the likely causal gene in this interval, and an activator of the antiviral response. Our approach charts an experimental and analytic path to decipher the mechanisms underlying genetic variation in other complex circuits in primary mammalian cells.
Publication Title
Deciphering molecular circuits from genetic variation underlying transcriptional responsiveness to stimuli.
Sample Metadata Fields
Age, Specimen part
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GSE11056- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone.
Publication Title
Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 656 Downloadable Samples
IlluminaHiSeq2500
Description
We introduced genome-wide pooled CRISPR-Cas9 libraries into primary mouse dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (TNF) by bacterial lipopolysaccharide (LPS), a key process in the host response to pathogens, mediated by the TLR4 pathway. We found many of the known regulators of TLR4 signaling, as well as dozens of previously unknown candidates that we validated. Overall design: We used stain base phenotype (staining for TNF) in order to search for negative and positive regulators of LPS response in differentiated BMDCs
Publication Title
A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
Protein expression is regulated by production and degradation of mRNAs and proteins, but their specific relationships remain unknown. We combine measurements of protein production and degradation and mRNA dynamics to build a quantitative genomic model of the differential regulation of gene expression in LPS stimulated mouse dendritic cells. Changes in mRNA abundance play a dominant role in determining most dynamic fold changes in protein levels. Conversely, the preexisting proteome of proteins performing basic cellular functions is remodeled primarily through changes in protein production or degradation, accounting for over half of the absolute change in protein molecules in the cell. Thus, the proteome is regulated by transcriptional induction of novel cellular functions and remodeling of preexisting functions through the protein life cycle. Overall design: Mouse primary dendritic cells were treated with LPS or mock stimulus and profiled over a 12-hour time course. Cells were grown in M-labeled SILAC media, which was replaced with H-labeled SILAC media at time 0. Aliquots were taken at 0, 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 hours post-stimulation and added to equal volumes of a master mix of unlabeled (L) cells for the purpose of normalization. RNA-Seq was performed at 0, 1, 2, 4, 6, 9, and 12 hours post-stimulation.
Publication Title
Immunogenetics. Dynamic profiling of the protein life cycle in response to pathogens.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 228 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Common genetic variants modulate pathogen-sensing responses in human dendritic cells.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 113 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Variation in individuals' responses to environmental factors is believed to influence susceptibility to complex diseases in humans. The genetic basis of such variation is poorly understood. We measured gene expression from resting and stimulated dendritic cells (DCs) derived from the peripheral blood of healthy individuals. We stimulated the primary DCs with E. coli lipopolysaccharide (LPS) or influenza virus. Using serial replicate samples, we selected genes that showed evidence of reproducibility within the serial replicates.
Publication Title
Common genetic variants modulate pathogen-sensing responses in human dendritic cells.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Mus musculus
- 96 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
mouse primary BMDCs were stimulated with tlr ligands and gene expression changes were profiled on Affymetrix arrays
Publication Title
Unbiased reconstruction of a mammalian transcriptional network mediating pathogen responses.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
We used microarrays to detail the global programme of gene expression underlying Polo-like kinase inhibition with BI 2536 compound in mouse bone marrow-derived dendritic cells (BMDCs) stimulated with Toll-like receptor agonists LPS and poly(I:C).
Publication Title
Systematic discovery of TLR signaling components delineates viral-sensing circuits.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Calyx of Held giant presynaptic terminals in the medial nucleus of the trapezoid body of the auditory brainstem form axosomatic synapses that have advanced to one of the best-studied synaptic system of the mammalian brain. As the auditory system matures and adjusts to high fidelity synaptic transmission, the calyx undergoes extensive structural and functional changes: it is formed around postnatal day 3 (P3), achieves immature function until hearing onset around P10 and can be considered mature from P21 onwards. This setting provides the unique opportunity to examine the repertoire of genes driving synaptic structure and function.
Publication Title
Gene expression profile during functional maturation of a central mammalian synapse.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 377 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from transverse slices of embryos from a variety of D. melanogaster mutants (bicoid over-expression, bicoid knockdown, hunchback knocdown, and zelda mutant) at the blastoderm stage to determine genome-wide patterns of gene expression. Overall design: mRNA from transverse sections of single D. melanogaster embryos mutant for patterning TFs was sequenced.
Publication Title
Genome-wide measurement of spatial expression in patterning mutants of <i>Drosophila melanogaster</i>.
Sample Metadata Fields
Specimen part, Subject
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