Sean M. Grimmond

Publications (2)9.68 Total impact

• Article: Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages.

  Kate Schroder, Katharine M Irvine, Martin S Taylor, Nilesh J Bokil, Kim-Anh Le Cao, Kelly-Anne Masterman, Larisa I Labzin, Colin A Semple, Ronan Kapetanovic, Lynsey Fairbairn, [......], Hideya Kawaji, Geoffrey J McLachlan, Nick Goldman, Sean M Grimmond, Piero Carninci, Harukazu Suzuki, Yoshihide Hayashizaki, Boris Lenhard, David A Hume, Matthew J Sweet
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  ABSTRACT: 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 interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)-4 agonist lipopolysaccharide (LPS). By 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 orthologues were identified as "divergently regulated"). We further demonstrate concordant regulation of human-specific LPS target genes in primary pig macrophages. Divergently regulated orthologues 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. Functional consequences of divergent gene regulation were confirmed by showing LPS pretreatment boosts subsequent TLR6 responses in mouse but not human macrophages, in keeping with mouse-specific TLR6 induction. Divergently regulated 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 interspecies promoter conservation. Thus, the genes controlled by complex, highly conserved promoters that facilitate dynamic regulation are also the most susceptible to evolutionary change.
  Proceedings of the National Academy of Sciences 03/2012; 109(16):E944-53. · 9.68 Impact Factor
• Article: Development of the Minimum Information Specification for in situ Hybridization and Immunohistochemistry Experiments (MISFISHIE)

  Eric W Deutsch, Catherine A Ball, G Steven Bova, Alvis Brazma, Roger E Bumgarner, David Campbell, Helen C Causton, Jeff Christiansen, Duncan Davidson, Lillian J Eichner, Young Ah Goo, Sean M. Grimmond, Thorsten Henrich, Michael H Johnson, M. Korb
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  ABSTRACT: We describe the creation process of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE). Modeled after the existing minimum information specification for microarray data, we created a new specification for gene expression localization experiments, initially to facilitate data sharing within a consortium. After successful use within the consortium, the specification was circulated to members of the wider biomedical research community for comment and refinement. After a period of acquiring many new suggested requirements, it was necessary to enter a final phase of excluding those requirements that were deemed inappropriate as a minimum requirement for all experiments. The full specification will soon be published as a version 1.0 proposal to the community, upon which a more full discussion must take place so that the final specification may be achieved with the involvement of the whole community. This paper is part of the special issue of OMICS on data standards.