The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Av. Ignacio Morones Prieto 3000 Pte, Col. Los Doctores, C.P. 64710, Monterrey, N.L., Mexico.
Nat Commun. 2019 Jul 19;10(1):3215. doi: 10.1038/s41467-019-11053-8.
The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1r mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1r mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r rodents. Csf1r mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals.
单核吞噬细胞的增殖、分化和存活依赖于巨噬细胞集落刺激因子受体（CSF1R）的信号。哺乳动物 Csf1r 基因座包含一个高度保守的超级增强子，即 fms 内含子调控元件（FIRE）。在这里，我们表明，在小鼠中删除 FIRE 会选择性地影响 CSF1R 的表达和特定组织中的组织巨噬细胞发育。删除 FIRE 会使鼠胚胎干细胞中的巨噬细胞发育缺失。Csf1r 小鼠在胚胎、大脑小神经胶质细胞和皮肤、肾脏、心脏和腹膜中的固有巨噬细胞中缺乏巨噬细胞。其他巨噬细胞群和单核细胞的稳态不受影响，但骨髓中的单核细胞及其祖细胞缺乏表面 CSF1R。最后，Csf1r 小鼠健康且可育，没有在 Csf1r 啮齿动物中报道的生长、神经或发育异常。因此，Csf1r 小鼠为探索成年动物中组织特异性巨噬细胞群的稳态、生理和免疫学功能提供了一个模型。
