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Publication : Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival.

First Author  Gautier EL Year  2014
Journal  J Exp Med Volume  211
Issue  8 Pages  1525-31
PubMed ID  25024137 Mgi Jnum  J:214723
Mgi Id  MGI:5603936 Doi  10.1084/jem.20140570
Citation  Gautier EL, et al. (2014) Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival. J Exp Med 211(8):1525-31
abstractText  The transcription factor Gata6 regulates proliferation and differentiation of epithelial and endocrine cells and cancers. Among hematopoietic cells, Gata6 is expressed selectively in resident peritoneal macrophages. We thus examined whether the loss of Gata6 in the macrophage compartment affected peritoneal macrophages, using Lyz2-Cre x Gata6(flox/flox) mice to tackle this issue. In Lyz2-Cre x Gata6(flox/flox) mice, the resident peritoneal macrophage compartment, but not macrophages in other organs, was contracted, with only a third the normal number of macrophages remaining. Heightened rates of death explained the marked decrease in peritoneal macrophage observed. The metabolism of the remaining macrophages was skewed to favor oxidative phosphorylation and alternative activation markers were spontaneously and selectively induced in Gata6-deficient macrophages. Gene expression profiling revealed perturbed metabolic regulators, including aspartoacylase (Aspa), which facilitates generation of acetyl CoA. Mutant mice lacking functional Aspa phenocopied the higher propensity to death and led to a contraction of resident peritoneal macrophages. Thus, Gata6 regulates differentiation, metabolism, and survival of resident peritoneal macrophages.
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