Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival.
Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival.
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DOI：
10.1084/jem.20140570
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发表时间：
2014-07-28
期刊：
影响因子：
--
通讯作者：
Randolph GJ
中科院分区：
文献类型：
--
作者：
Gautier EL;Ivanov S;Williams JW;Huang SC;Marcelin G;Fairfax K;Wang PL;Francis JS;Leone P;Wilson DB;Artyomov MN;Pearce EJ;Randolph GJ
Gata6 调节腹膜巨噬细胞的分化、代谢和存活。转录因子 Gata6 调节上皮细胞和内分泌细胞以及癌症的增殖和分化。在造血细胞中，Gata6 在常驻腹膜巨噬细胞中选择性表达。因此，我们使用 Lyz2-Cre x Gata6flox/flox 小鼠来检查巨噬细胞室中 Gata6 的丢失是否影响腹膜巨噬细胞来解决这个问题。在 Lyz2-Cre x Gata6flox/flox 小鼠中，常驻腹膜巨噬细胞室收缩，但其他器官中的巨噬细胞没有收缩，仅剩余正常数量的三分之一。死亡率升高解释了观察到的腹膜巨噬细胞的显着减少。其余巨噬细胞的代谢偏向于氧化磷酸化，并且在 Gata6 缺陷型巨噬细胞中自发且选择性地诱导替代激活标记物。基因表达谱分析揭示了代谢调节因子受到干扰，包括天冬氨酸酰化酶 (Aspa)，它促进乙酰辅酶 A 的生成。缺乏功能性 Aspa 的突变小鼠表现出更高的死亡倾向，并导致腹膜巨噬细胞收缩。因此，Gata6 调节腹膜巨噬细胞的分化、代谢和存活。
Gata6 regulates differentiation, metabolism and survival of peritoneal macrophages. 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 Gata6flox/flox mice to tackle this issue. In Lyz2-Cre x Gata6flox/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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影响因子：
64.5
作者：
Haldar M;Kohyama M;So AY;Kc W;Wu X;Briseño CG;Satpathy AT;Kretzer NM;Arase H;Rajasekaran NS;Wang L;Egawa T;Igarashi K;Baltimore D;Murphy TL;Murphy KM
通讯作者：
Murphy KM
影响因子：
20.3
作者：
Gautier, Emmanuel L.;Ivanov, Stoyan;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
29
作者：
Vats, Divya;Mukundan, Lata;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I