Plenary perspective: the complexity of constitutive and inducible gene expression in mononuclear phagocytes - PubMed (original) (raw)

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Plenary perspective: the complexity of constitutive and inducible gene expression in mononuclear phagocytes

David A Hume. J Leukoc Biol. 2012 Sep.

Abstract

Monocytes and macrophages differentiate from progenitor cells under the influence of colony-stimulating factors. Genome-scale data have enabled the identification of the set of genes that distinguishes macrophages from other cell types and the ways in which thousands of genes are regulated in response to pathogen challenge. Although there has been a focus on a small subset of lineage-enriched transcription factors, such as PU.1, more than one-half of the transcription factors in the genome can be expressed in macrophage lineage cells under some state of activation, and they interact in a complex network. The network architecture is conserved across species, but many of the target genes evolve rapidly and differ between mouse and human. The data and publication deluge related to macrophage biology require the development of new analytical tools and ways of presenting information in an accessible form.

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Figures

Figure 1.

Figure 1.. Dynamic regulation of gene expression in macrophages.

This figure shows unpublished data that formed the basis for initial identification of LPS-inducible genes in human monocytes [68]. It is shown solely to illustrate the pattern seen in a global analysis of macrophage biology. In this experiment, human blood monocytes were first differentiated in CSF-1 for 7 days to generate MDMs and then stimulated for the times indicated with a maximal dose of bacterial LPS. Gene expression for the whole time course was normalized to one in the MDM; curves for genes that were down-regulated during differentiation are colored red, and those that are up-regulated are colored green. The notable features are the very large dynamic range and extent of regulation and the apparent balance between activation and repression. Note also that there is no consistent pattern for the genes coded red and green in their subsequent response to LPS.

Figure 2.

Figure 2.. Expression of key myeloid transcription factors.

The images are screen shots of part of the display on the website

www.biogps.org

for the transcription factors indicated. Note that PU.1 is most highly expressed in the macrophages, osteoclasts, isolated microglia, and the macrophage line RAW264 and much lower in granulocytes, B cells, and DCs. MITF is shared by macrophages, mast cells, and retinal pigment epithelium. The MITF-related transcription factor TFEC is also macrophage-restricted, except for a previously unreported expression in myeloid progenitors. BATF3 is expressed at high levels only in the myeloid DCs.

Figure 2.

Figure 2.. Expression of key myeloid transcription factors.

The images are screen shots of part of the display on the website

www.biogps.org

for the transcription factors indicated. Note that PU.1 is most highly expressed in the macrophages, osteoclasts, isolated microglia, and the macrophage line RAW264 and much lower in granulocytes, B cells, and DCs. MITF is shared by macrophages, mast cells, and retinal pigment epithelium. The MITF-related transcription factor TFEC is also macrophage-restricted, except for a previously unreported expression in myeloid progenitors. BATF3 is expressed at high levels only in the myeloid DCs.

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