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The Transcription Factor Gata6 Links Tissue Macrophage Phenotype and Proliferative Renewal

Science  09 May 2014:
Vol. 344, Issue 6184, pp. 645-648
DOI: 10.1126/science.1251414

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Gata6 Controls Peritoneal Macs

Macrophages seed tissues throughout the body and are shaped both phenotypically and functionally by the microenvironment they inhabit. Despite such heterogeneity, most tissue macrophages self-renew by local proliferation. How this is regulated, however, is unclear. Rosas et al. (p. 645, published online 24 April) used gene expression analysis to show that the transcription factor Gata6 is specifically expressed in peritoneal macrophages. Gata6 was critical for maintaining the transcriptional signature of peritoneal macrophages and for their proliferative renewal during homeostasis and under inflammatory conditions.

Abstract

Tissue-resident macrophages are heterogeneous as a consequence of anatomical niche–specific functions. Many populations self-renew independently of bone marrow in the adult, but the molecular mechanisms of this are poorly understood. We determined a transcriptional profile for the major self-renewing population of peritoneal macrophages in mice. These cells specifically expressed the transcription factor Gata6. Selective deficiency of Gata6 in myeloid cells caused substantial alterations in the transcriptome of peritoneal macrophages. Gata6 deficiency also resulted in dysregulated peritoneal macrophage proliferative renewal during homeostasis and in response to inflammation, which was associated with delays in the resolution of inflammation. Our investigations reveal that the tissue macrophage phenotype is under discrete tissue-selective transcriptional control and that this is fundamentally linked to the regulation of their proliferation renewal.

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