Chapter 8 : Transcriptional Regulation and Macrophage Differentiation

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The mononuclear phagocyte system (MPS) was originally defined by van Furth and Cohn ( ) as a family of cells of the innate immune system derived from hematopoietic progenitor cells under the influence of specific growth factors ( ). Differentiated cells of the MPS, monocytes and macrophages, are effectors of innate immunity, engulfing and killing pathogens. They are also needed for tissue repair and resolution of inflammation and for the generation of an appropriate acquired immune response. Their biology and differentiation have been reviewed by a number of authors ( ). The original definition of the MPS considered an essentially linear sequence from pluripotent progenitors, through committed myeloid progenitors shared with granulocytes, to promonocytes and blood monocytes, and thence to tissue macrophages ( ). Resident macrophages differ in function between tissues, and within tissues they occupy a specific niche ( ). In some locations, for example, associated with epithelia, they clearly have individual identifiable territories that form a regular pattern ( ).

Citation: Hume D, Summers K, Rehli M. 2017. Transcriptional Regulation and Macrophage Differentiation, p 119-139. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0024-2015
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Figure 1

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 ( ). 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).

Citation: Hume D, Summers K, Rehli M. 2017. Transcriptional Regulation and Macrophage Differentiation, p 119-139. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0024-2015
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Figure 2

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 ( ).

Citation: Hume D, Summers K, Rehli M. 2017. Transcriptional Regulation and Macrophage Differentiation, p 119-139. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0024-2015
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Figure 3

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 and . The mouse PU.1 track is derived from reference , and other mouse tracks from ENCODE.

Citation: Hume D, Summers K, Rehli M. 2017. Transcriptional Regulation and Macrophage Differentiation, p 119-139. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0024-2015
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