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Publication : Early Fate Defines Microglia and Non-parenchymal Brain Macrophage Development.

First Author  Utz SG Year  2020
Journal  Cell Volume  181
Issue  3 Pages  557-573.e18
PubMed ID  32259484 Mgi Jnum  J:292317
Mgi Id  MGI:6442058 Doi  10.1016/j.cell.2020.03.021
Citation  Utz SG, et al. (2020) Early Fate Defines Microglia and Non-parenchymal Brain Macrophage Development. Cell 181(3):557-573.e18
abstractText  Central nervous system (CNS) macrophages comprise microglia and border-associated macrophages (BAMs) residing in the meninges, the choroid plexus, and the perivascular spaces. Most CNS macrophages emerge during development, with the exception of choroid plexus and dural macrophages, which are replaced by monocytes in adulthood. Whether microglia and BAMs share a developmental program or arise from separate lineages remains unknown. Here, we identified two phenotypically, transcriptionally, and locally distinct brain macrophages throughout development, giving rise to either microglia or BAMs. Two macrophage populations were already present in the yolk sac suggesting an early segregation. Fate-mapping models revealed that BAMs mostly derived from early erythro-myeloid progenitors in the yolk sac. The development of microglia was dependent on TGF-beta, whereas the genesis of BAMs occurred independently of this cytokine. Collectively, our data show that developing parenchymal and non-parenchymal brain macrophages are separate entities in terms of ontogeny, gene signature, and requirement for TGF-beta.
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