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E-GEOD-19490 - Transcriptional responses of mouse BMM and TEPM to lipopolysaccharide (LPS)

Status
Released on 28 March 2012, last updated on 27 June 2012
Organism
Mus musculus
Samples (24)
Array (1)
Protocols (8)
Description
Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune diversification by analyzing inter-species differences in the transcriptional responses of primary human and mouse macrophages to the TLR4 agonist, LPS. Using a custom platform permitting cross-species interrogation coupled with deep sequencing of mRNA 5’ ends, we identified extensive divergence in LPS-regulated orthologous gene expression between humans and mice (24% of orthologs, http://www.macgate.qfab.org). Divergently regulated (DR) orthologs were enriched for genes encoding cellular “inputs” such as cell surface receptors (e.g. TLR6, IL-7Rα), and functional “outputs” such as inflammatory cytokines/chemokines (e.g. CCL20, CXCL13). Conversely, intracellular signaling components linking inputs to outputs were typically concordantly regulated. DR genes were associated with a large dynamic range of gene expression, and specific promoter architectural features (TATA box enrichment, CpG island depletion). Surprisingly, regulatory divergence was also associated with enhanced inter-species promoter conservation. Thus, the genes controlled by complex, highly conserved promoters that facilitate dynamic regulation are also the most susceptible to evolutionary change. Mouse macrophages (bone marrow-derived macrophages, BMM and thioglycollate-elicited peritoneal macrophages, TEPM) were stimulated with the TLR4 agonist, lipopolysaccharide, over a time course (0, 2, 6, 24h) and analysed in biological triplicate on a custom-designed, focused microarray.
Experiment type
transcription profiling by array 
Contacts
Kate Schroder, Katharine Irvine, Matthew J Sweet
Citation
Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages. Schroder K, Irvine KM, Taylor MS, Bokil NJ, Le Cao KA, Masterman KA, Labzin LI, Semple CA, Kapetanovic R, Fairbairn L, Akalin A, Faulkner GJ, Baillie JK, Gongora M, Daub CO, Kawaji H, McLachlan GJ, Goldman N, Grimmond SM, Carninci P, Suzuki H, Hayashizaki Y, Lenhard B, Hume DA, Sweet MJ. , PMID:22451944
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-19490.idf.txt
Sample and data relationshipE-GEOD-19490.sdrf.txt
Raw data (1)E-GEOD-19490.raw.1.zip
Processed data (1)E-GEOD-19490.processed.1.zip
Array designA-GEOD-9802.adf.txt
Links