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Transcriptional Regulation and Macrophage Differentiation

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  • Authors: David A. Hume1, Kim M. Summers2, Michael Rehli3
  • Editor: Siamon Gordon4
    Affiliations: 1: University of Edinburgh, The Roslin Institute and Royal (Dick) School of Veterinary Studies, Midlothian EH25 9RG, United Kingdom; 2: University of Edinburgh, The Roslin Institute and Royal (Dick) School of Veterinary Studies, Midlothian EH25 9RG, United Kingdom; 3: University Hospital Regensburg, Department of Internal Medicine III, D-93047 Regensburg, Germany; 4: Oxford University, Oxford, United Kingdom
  • Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0024-2015
  • Received 14 October 2015 Accepted 23 October 2015 Published 03 June 2016
  • David A. Hume, [email protected]
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  • Abstract:

    Monocytes and macrophages are professional phagocytes that occupy specific niches in every tissue of the body. Their survival, proliferation, and differentiation are controlled by signals from the macrophage colony-stimulating factor receptor (CSF-1R) and its two ligands, CSF-1 and interleukin-34. In this review, we address the developmental and transcriptional relationships between hematopoietic progenitor cells, blood monocytes, and tissue macrophages as well as the distinctions from dendritic cells. A huge repertoire of receptors allows monocytes, tissue-resident macrophages, or pathology-associated macrophages to adapt to specific microenvironments. These processes create a broad spectrum of macrophages with different functions and individual effector capacities. The production of large transcriptomic data sets in mouse, human, and other species provides new insights into the mechanisms that underlie macrophage functional plasticity.

  • Citation: Hume D, Summers K, Rehli M. 2016. Transcriptional Regulation and Macrophage Differentiation. Microbiol Spectrum 4(3):MCHD-0024-2015. doi:10.1128/microbiolspec.MCHD-0024-2015.


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Monocytes and macrophages are professional phagocytes that occupy specific niches in every tissue of the body. Their survival, proliferation, and differentiation are controlled by signals from the macrophage colony-stimulating factor receptor (CSF-1R) and its two ligands, CSF-1 and interleukin-34. In this review, we address the developmental and transcriptional relationships between hematopoietic progenitor cells, blood monocytes, and tissue macrophages as well as the distinctions from dendritic cells. A huge repertoire of receptors allows monocytes, tissue-resident macrophages, or pathology-associated macrophages to adapt to specific microenvironments. These processes create a broad spectrum of macrophages with different functions and individual effector capacities. The production of large transcriptomic data sets in mouse, human, and other species provides new insights into the mechanisms that underlie macrophage functional plasticity.

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Expression of selected genes encoding myeloid-restricted growth factor receptors. Stacked bars show expression of each gene in the cell type (normalized tags per million) derived from FANTOM5 CAGE data for human cells ( 107 ). Cell types are presented in the order of maturation: CD34 MSCs; CMPs; GMPs; migratory DCs; CD14 monocytes (CD14 Mo); CD14CD16 monocytes (CD14, CD16 Mo); CD16 monocytes (CD16 Mo); MDMs (cultured in CSF-1); monocytes cultured in GM-CSF (MDCs); and migratory DCs from skin lymphatics (LC).

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0024-2015
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Network layout of 108 growth factor receptor and transcription factor genes in myeloid lineages. Nodes represent genes and edges correlation between expression patterns of genes at a Pearson correlation coefficient of 0.74 or greater. Nodes of the same color form a cluster. Histograms show the average expression pattern of genes within the cluster. axis, cell type. Each column represents one cell type, presented in the order of maturation: CD34 mesenchymal stem cells; CMPs; GMPs; migratory DCs; CD14 monocytes; CD14CD16 monocytes; CD16 monocytes; MDMs (cultured in CSF-1); monocytes cultured in GM-CSF; and migratory DCs from skin lymphatics. Column colors are the same as the nodes in the cluster. axis, average expression of genes in the cluster (normalized tags per million) derived from FANTOM5 CAGE data for human cells ( 107 ).

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0024-2015
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Chromatin architecture of the mouse and human loci. Genome browser tracks of indicated histone modifications and transcription factors associated with enhancer elements are shown. The filled green box indicates the macrophage promoter. Boxes in blue identify intergenic and intragenic enhancer candidates. FIRE is represented by a filled blue box. Chip-Seq data sets that formed the basis of this figure for human macrophages are from derived from references 104 and 159 . The mouse PU.1 track is derived from reference 136 , and other mouse tracks from ENCODE.

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0024-2015
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Coexpression of transcription factor genes in cells of myeloid lineages

Source: microbiolspec June 2016 vol. 4 no. 3 doi:10.1128/microbiolspec.MCHD-0024-2015

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