小胶质细胞和BAM不同的命运决定
2020-04-13   阅读:635   来源:细胞

瑞士苏黎世大学Melanie Greter研究组揭示,早期命运定义了小胶质细胞和非实质性脑巨噬细胞的发育。202046日《细胞》杂志发表了这一成果。

他们在整个发育过程中鉴定出两个表型上、转录上和局部上不同的脑巨噬细胞,能够产生小胶质细胞或边界相关的巨噬细胞(BAM)。卵黄囊中已经有两个巨噬细胞群体,表明在早期进行分离。

命运映射模型显示,BAM主要来自卵黄囊中的早期红系-髓系祖细胞。小胶质细胞的形成依赖于TGF-β,而BAMs的发生独立于该细胞因子。

总体而言,他们的数据表明,就个体发育、基因标签和对TGF-β的需求而言,发育中的实质性和非实质性脑巨噬细胞是独立的实体。

据了解,中枢神经系统(CNS)巨噬细胞包括小胶质细胞和BAM,它们位于边界、脑膜、脉络丛和血管周间隙中。除脉络丛和硬脑膜巨噬细胞在成年期被单核细胞所取代外,大多数中枢神经系统巨噬细胞在发育过程中出现。小胶质细胞和BAM是否共享一个发育进程还是由不同的谱系产生仍然未知。

附:英文原文

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

Author: Sebastian G. Utz, Peter See, Wiebke Mildenberger, Morgane Sonia Thion, Aymeric Silvin, Mirjam Lutz, Florian Ingelfinger, Nirmala Arul Rayan, Iva Lelios, Anne Buttgereit, Kenichi Asano, Shyam Prabhakar, Sonia Garel, Burkhard Becher, Florent Ginhoux, Melanie Greter

Issue&Volume: 2020-04-06

Abstract: Central nervous system (CNS) macrophages comprise microglia and border-associatedmacrophages (BAMs) residing in the meninges, the choroid plexus, and the perivascularspaces. Most CNS macrophages emerge during development, with the exception of choroidplexus and dural macrophages, which are replaced by monocytes in adulthood. Whethermicroglia and BAMs share a developmental program or arise from separate lineages remainsunknown. Here, we identified two phenotypically, transcriptionally, and locally distinctbrain macrophages throughout development, giving rise to either microglia or BAMs.Two macrophage populations were already present in the yolk sac suggesting an earlysegregation. Fate-mapping models revealed that BAMs mostly derived from early erythro-myeloidprogenitors in the yolk sac. The development of microglia was dependent on TGF-β,whereas the genesis of BAMs occurred independently of this cytokine. Collectively,our data show that developing parenchymal and non-parenchymal brain macrophages areseparate entities in terms of ontogeny, gene signature, and requirement for TGF-β.

DOI: 10.1016/j.cell.2020.03.021

编辑:小柯机器人

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