BioGPS is one example of a new era of emerging user-friendly portals see text footnote 1 that enable the analysis of complex transcriptomic data. Development and function of dendritic cell subsets. At a single cell level, there is essentially bimodal variation; genes are either induced by LPS or they are not Macrophages from different mouse strains differ substantially in their gene expression profiles 58 , 61 , Many transcription factors were rapidly repressed during the differentiation of THP-1 cells. At top right, we see that three of the distal promoters were induced by LPS in human monocyte-derived macrophages, starting around 3—4 h after stimulation. This article is part of the Research Topic Cells, signalling pathways and systems:
In macrophages, the gene clusters include lineage-specific genes, interferon-responsive genes, early inflammatory genes, and genes required for endocytosis and lysosome function. Negative regulation of toll-like receptor-mediated immune responses. Challenges to the unified concept of an MPS have been discussed elsewhere 4 , 5 , 8. The most controversial distinction in this respect is between macrophages and dendritic cells DC. PLoS Comput Biol 3:
At a single cell level, there is essentially bimodal variation; genes are either induced by LPS or they are not Several of these factors have well-documented repressive roles.
In essence, when dealing with an ever-changing pathogen landscape, it is desirable not to have all the macrophage eggs in one basket. The human alpha 1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes.
We compared the motif over-representation in the promoters of LPS-inducible macrophage genes in humans and mice BMC Immunol 4: They also identified the stress response factors, NRF1 and NRF2, as candidate regulators, based upon the presence of binding site motifs in active promoters Conservation and divergence in toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages.
IFITM3 restricts the morbidity and mortality associated with influenza. Unfortunately, there is absolutely no support for the usefulness of markers in genome-scale data. The FANTOM5 consortium produced data that enable promoter-based clustering of co-expression networks, which support the same distinction between two 2031-14 classes of APC 40 Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.
Although some of this variation could arise through covariance of transcription factor expression, the major driver of heterogeneity is the intrinsic probabilistic nature of transcriptional regulation They are the front line innate defense against pathogens, drive appropriate acquired immune responses, initiate inflammation, and promote resolution and repair. jume
The motifs over-represented in the promoters, and their relative over-representation, was conserved suggesting that in both species the promoters sample a common transcriptional milieu.
Around two-thirds of all transcription factors can be detected in primary macrophages, and they form a scale-free or small-world interaction network Indeed, the LPS receptor, TLR4is expressed from only one allele in individual cells, with an allele-counting mechanism similar to that of the X chromosome Genes Dev Mol Cell With completed genomes, comparable datasets are becoming available species such as the domestic pig, chickens, sheep, and cattle.
Pattern recognition receptors and inflammation.
Methods for analyzing deep sequencing expression data: Negative regulation of toll-like receptor-mediated immune responses. In microarray datasets from mouse and human 2728cells annotated as DC form two distinct clusters.
Nearly half of all transcription factors were detected at some time point during differentiation and around were dynamically regulated.
TFEC is a macrophage-restricted member of the microphthalmia-TFE subfamily of basic helix-loop-helix leucine zipper transcription factors.
Frontiers | The Many Alternative Faces of Macrophage Activation | Immunology
Curr Opin Rheumatol The second most abundant TSS, p3 serpinA1, was constitutively active in granulocytes. The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide.
Fate mapping analysis reveals that adult microglia derive from primitive macrophages. The function of myb, in particular, correlates with its known downregulation as progenitor cells differentiate and exit the cell cycle 1and its ability to hum macrophage differentiation and to directly repress csf1r transcription Gene expression patterns in blood leukocytes discriminate patients with acute infections.
Gosselin D, Glass CK. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Modular transcriptional repertoire analyses of adults with systemic lupus erythematosus reveal distinct type I and type II interferon signatures.