Origin, fate and dynamics of macrophages at central nervous system interfaces.
Origin, fate and dynamics of macrophages at central nervous system interfaces.
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DOI：
10.1038/ni.3423
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发表时间：
2016-07
影响因子：
30.5
通讯作者：
Prinz M
中科院分区：
文献类型：
--
作者：
Goldmann T;Wieghofer P;Jordão MJ;Prutek F;Hagemeyer N;Frenzel K;Amann L;Staszewski O;Kierdorf K;Krueger M;Locatelli G;Hochgerner H;Zeiser R;Epelman S;Geissmann F;Priller J;Rossi FM;Bechmann I;Kerschensteiner M;Linnarsson S;Jung S;Prinz M
血管周围、脑膜和脉络丛巨噬细胞是在脑边界介导免疫应答的非实质巨噬细胞。虽然实质小胶质细胞的起源最近已经阐明，少得多是已知的前体，潜在的转录程序和其他巨噬细胞在中枢神经系统（CNS）的动力学。据推测，它们与血液传播的单核细胞具有高周转率。然而，大规模的单细胞RNA测序揭示了血管周围巨噬细胞和小胶质细胞而不是单核细胞之间的惊人的分子重叠。使用几种命运映射方法和联体共生，我们证明了中枢神经系统巨噬细胞产生于胚胎发育过程中的卵黄囊前体，并保持稳定的人口。值得注意的是，CNS巨噬细胞的产生依赖于转录因子Pu.1，而myb、Batf3和Nr4a1不是必需的。在自身免疫性炎症时，巨噬细胞通过局部增殖进行广泛的自我更新。我们的数据为大脑先天免疫系统提供了具有挑战性的新见解。
Perivascular, meningeal and choroid plexus macrophages are non-parenchymal macrophages that mediate immune responses at brain boundaries. Although the origin of parenchymal microglia has recently been elucidated, much less is known about the precursors, the underlying transcriptional program and the dynamics of the other macrophages in the central nervous system (CNS). It has been assumed that they have a high turnover with blood-borne monocytes. However, large scale single-cell RNA-sequencing reveals a striking molecular overlap between perivascular macrophages and microglia but not monocytes. Using several fate mapping approaches and parabiosis we demonstrate that CNS macrophages arise from yolk sac precursors during embryonic development and remain a stable population. Notably, the generation of CNS macrophages relies on the transcription factor Pu.1 whereas myb, Batf3 and Nr4a1 are not required. Upon autoimmune inflammation, macrophages undergo extensive self-renewal by local proliferation. Our data provide challenging new insights into brains innate immune system.