Journal Article

The Transcription Factor Gata6 Links Tissue Macrophage Phenotype and Proliferative Renewal

Jones, Simon A., Davies, Luke C., Taylor, Philip R., Giles, Peter J., O'Donnell, Valerie B., Fraser, Donald J., Rosas, Marcela, Liao, Chia-Te, Kharfan, Bashar, Stone, Timothy C.

2014

Overview

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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Bacteriophages / Bone marrow / Cell Proliferation / GATA6 Transcription Factor - genetics / GATA6 Transcription Factor - physiology / Gene expression / Genotype & phenotype / Heterogeneity / Immunity / Inflammation / Inflammation - immunology / Macroecology / Macrophages / Macrophages, Peritoneal - immunology / Mice / Mice, Knockout / Myeloid cells / Myeloid Cells - immunology / Peritoneal macrophages / Phenotype / Phenotypes / Quantification / Seeds / Tissues / Transcription factors