Project description:This SuperSeries is composed of the following subset Series: GSE19482: Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS) GSE19490: Transcriptional responses of mouse BMM and TEPM to lipopolysaccharide (LPS) GSE19765: Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS) - Illumina arrays GSE19766: Transcriptional responses of mouse bone marrow-derived macrophages (BMM) to lipopolysaccharide (LPS) - Illumina arrays Refer to individual Series
Project description:These microarrays were performed for use in a genome-wide scan for LPS-regulated genes in human monocyte-derived macrophages, in order to construct a list of LPS-regulated genes for detailed interrogation on custom microarrays (see GSE19482 for custom array analysis). Human monocyte-derived macrophages (HMDM) were stimulated with the TLR4 agonist, lipopolysaccharide, over a time course (0, 0.5, 2, 6, 24h) and analysed in biological duplicate (each of which represents a pool of two independent blood donors), in total representing 4 macrophage preparations from independent blood donors, by commercial Illumina microarray.
Project description:Comparison of human monocyte derived dendritic cell transcriptional responses to stimulation with lipopolysaccharide (LPS), Mycobacterium vaccae (MV) and Pam3CSK4 (PCSK)
Project description:Macrophages (Mɸ) are highly heterogenous and versatile innate immune cells involved in homeostatic and immune responses. Activated Mɸ can exist in two extreme phenotypes: pro-inflammatory (M1) and anti-inflammatory (M2) Mɸ and these phenotypes can be recapitulated in vitro by using lipopolysaccharide (LPS) plus IFNγ and IL-4, respectively. In the recent years, human induced pluripotent stem cells (iPSC) derived-Mɸ have gained major attention since they are functionally similar to human monocyte derived-Mɸ and are receptive to genome editing. We performed quantitative proteomics of culture supernatants to identify soluble factors released from differentially polarised iPSC-derived Mɸ (iPSDM). Our analysis suggests that the cytokine/chemokine profiles released from polarised iPSDM are similar to monocyte-derived Mɸ.
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.
Project description:Macrophages (Mɸ) are highly heterogenous and versatile innate immune cells involved in homeostatic and immune responses. Activated Mɸ can exist in two extreme phenotypes: pro-inflammatory (M1) and anti-inflammatory (M2) Mɸ and these phenotypes can be recapitulated in vitro by using lipopolysaccharide (LPS) plus IFNγ and IL-4, respectively. In the recent years, human induced pluripotent stem cells (iPSC) derived-Mɸ have gained major attention since they are functionally similar to human monocyte derived-Mɸ and are receptive to genome editing. In this study, we used quantitative proteomics to address whether the plasticity of iPSC-derived Mɸ (iPSDM) are similar to human monocyte derived Mɸ. Our analyses suggest that iPSC Mɸ are promising tools to understand Mɸ biology since they exhibit similar polarisation profiles and functions as monocyte-derived Mɸ. We believe this comprehensive proteome data set will be a useful resource in the Mɸ field.
Project description:We measured TNFα activity on the transcriptional level by identifying TNFα-inducible genes in human blood monocyte-derived macrophages (MDM). On the basis that TNFα does not act in isolation, we used bacterial lipopolysaccharide (LPS) as a prototypic model of a stimulus to invoke secretion of a wide range of immunologically active factors, including TNFα. In order to identify gene expression attributable to LPS-induced TNFα, we compared the transcriptome of MDM 24 hours after stimulation with 100 ng/ml ultra-pure LPS in the presence and absence of the soluble TNF receptor fusion protein Etanercept (10 µg/ml).
