Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE19482 | GEO | 2012/03/29
SECONDARY ACCESSION(S): PRJNA123949
REPOSITORIES: GEO
Similar Datasets
Project 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 5M-bM-^@M-^Y 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 M-bM-^@M-^\inputsM-bM-^@M-^] such as cell surface receptors (e.g. TLR6, IL-7RM-NM-1), and functional M-bM-^@M-^\outputsM-bM-^@M-^] 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. 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.
2012-03-28 | E-GEOD-19482 | biostudies-arrayexpress
Project 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.
2012-03-29 | GSE19490 | GEO
Project 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 5M-bM-^@M-^Y 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 M-bM-^@M-^\inputsM-bM-^@M-^] such as cell surface receptors (e.g. TLR6, IL-7RM-NM-1), and functional M-bM-^@M-^\outputsM-bM-^@M-^] 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.
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2011-12-09 | E-GEOD-23577 | biostudies-arrayexpress
Project description:Variation in gene regulation is thought to have played an important role in the evolution of primates, and many studies have documented differences in mRNA expression levels across primate species. However, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are more directly tied to phenotypic differences. To address this question, we used high-resolution, quantitative mass spectrometry to collect thousands of protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (LCLs). We also used RNA sequencing to collect transcript expression data from the same samples. Considering the two datasets jointly we found that there is much more inter-species divergence at the mRNA level than at the protein level. Remarkably, we found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest a much stronger evolutionary constraint on protein expression levels than on mRNA levels. We conclude that inter-species mRNA expression differences may often have limited functional consequences due to either buffering or compensatory changes in post-transcriptional or posttranslational regulation of proteins. Gene expression patterns were compared between human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (5 individuals from each species) using RNA-Seq. These gene expression patterns were also compared to protein expression patterns based on mass-spec data, which are available separately (see publication for details).
2013-10-17 | E-GEOD-49682 | biostudies-arrayexpress
Project description:Variation in gene regulation is thought to have played an important role in the evolution of primates, and many studies have documented differences in mRNA expression levels across primate species. However, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are more directly tied to phenotypic differences. To address this question, we used high-resolution, quantitative mass spectrometry to collect thousands of protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines (LCLs). We also used RNA sequencing to collect transcript expression data from the same samples. Considering the two datasets jointly we found that there is much more inter-species divergence at the mRNA level than at the protein level. Remarkably, we found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest a much stronger evolutionary constraint on protein expression levels than on mRNA levels. We conclude that inter-species mRNA expression differences may often have limited functional consequences due to either buffering or compensatory changes in post-transcriptional or posttranslational regulation of proteins.
2013-10-17 | GSE49682 | GEO
Project description:We describe the genome-wide nucleosome profiles of four related yeast species. All species display the same global organization features first described in S. cerevisiae: a stereotypical nucleosome organization along genes, and the classification of promoters into these which contain or lack a pronounced Nucleosome Depleted region (NDR), with the latter displaying a more dynamic pattern of gene expression. This global similarity, however, does not reflect a static evolutionary pattern, as nucleosome positioning at specific genes diverged rapidly leaving practically no similarity between S. cerevisiae and C. glabrata orthologs (~50 Myr). We show that this rapid divergence in nucleosome positioning contrasts a conserved pattern of gene expression, consistent with the idea that divergence of nucleosome patterns has a limited effect on gene expression as many different configurations can support the same regulatory outcome.
2011-12-09 | GSE23577 | GEO
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