The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal.
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.
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Marcela
M
Rosas
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Luke C
LC
Davies
Central Biotechnology Services, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Peter J
PJ
Giles
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Chia-Te
CT
Liao
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Bashar
B
Kharfan
Central Biotechnology Services, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Timothy C
TC
Stone
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Valerie B
VB
O'Donnell
Institute of Molecular Medicine, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Donald J
DJ
Fraser
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Simon A
SA
Jones
Cardiff Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, CF14 4XN, UK.
Philip R
PR
Taylor
D000818:Animals; D049109:Cell Proliferation; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology; D010641:Phenotype
D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse