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| Status |
Public on Mar 29, 2012 |
| Title |
Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Human monocyte-derived macrophages (HMDM) were stimulated with the TLR4 agonist, lipopolysaccharide, over a time course (0, 2, 6, 24h) and analysed in biological quadruplicate (each of which represents a pool of two independent blood donors), in total representing 8 macrophage preparations from independent blood donors, on a custom-designed, focused microarray.
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| Contributor(s) |
Schroder K, Irvine KM, Sweet MJ |
| Citation(s) |
22451944 |
| |
| Submission date |
Dec 15, 2009 |
| Last update date |
Mar 31, 2012 |
| Contact name |
Kate Schroder |
| E-mail(s) |
K.Schroder@imb.uq.edu.au
|
| Phone |
+617 33462087
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| Fax |
+617 33462101
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| Organization name |
Institute for Molecular Bioscience
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| Street address |
University of Queensland, St Lucia
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| City |
Brisbane |
| State/province |
QLD |
| ZIP/Postal code |
4072 |
| Country |
Australia |
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| Platforms (1) |
| GPL9801 |
Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE19492 |
Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages |
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| Relations |
| BioProject |
PRJNA123949 |
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