title: Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival.
abstract: 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.
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Ivanov
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Jesse W
authors.initials: JW
authors.lastname: Williams
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Stanley Ching-Cheng
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Medicine, Albert Einstein School of Medicine, Bronx, NY 10461.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Marcelin
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Keke
authors.initials: K
authors.lastname: Fairfax
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Francis
authors.affiliation: Department of Cell Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084.
authors.forename: Paola
authors.initials: P
authors.lastname: Leone
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: David B
authors.initials: DB
authors.lastname: Wilson
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Artyomov
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Pearce
authors.affiliation: Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110 grandolph@path.wustl.edu.
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002452:Cell Count; D002470:Cell Survival; D050993:GATA6 Transcription Factor / Q000172:deficiency / Q000378:metabolism*; D005786:Gene Expression Regulation; D008262:Macrophage Activation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D000581:Amidohydrolases; C019751:aspartoacylase