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研究揭示中枢神经系统巨噬细胞亚群的发生轨迹
2022-04-23 15:45

德国弗莱堡大学Marco Prinz课题组发现中枢神经系统(CNS)特异性巨噬细胞亚群在特定小生境中产生。相关论文于2022年4月20日发表在《自然》杂志上。

研究人员使用命运映射系统、单细胞分析和细胞特异性突变体相结合方法发现,只有脑膜巨噬细胞和小胶质细胞是来源于同一个产前祖细胞。相比之下,血管周围巨噬细胞仅在出生后以整合素依赖的方式从围产期脑膜巨噬细胞分化而来。血管周围巨噬细胞的建立需要动脉血管平滑肌细胞的存在。总之,该研究揭示了中枢神经系统中不同位置巨噬细胞亚群产生的精确发生过程。

据悉,CNS的所有组织驻留巨噬细胞-包括实质小胶质细胞,以及CNS相关巨噬细胞(CAMs1),如脑膜和血管周围巨噬细胞-都是CNS内源性先天免疫系统的一部分,是感染或创伤后的第一道免疫防线。有人提出,小胶质细胞和CAM的所有亚群都来源于卵黄囊中的产前细胞,这些细胞都来源早期红细胞系祖细胞。然而,人们对精确的个体发生关系、潜在的转录程序和驱动不同原位CAM亚群产生的分子信号知之甚少。

附:英文原文

Title: Specification of CNS macrophage subsets occurs postnatally in defined niches

Author: Masuda, Takahiro, Amann, Lukas, Monaco, Gianni, Sankowski, Roman, Staszewski, Ori, Krueger, Martin, Del Gaudio, Francesca, He, Liqun, Paterson, Neil, Nent, Elisa, Fernndez-Klett, Francisco, Yamasaki, Ayato, Frosch, Maximilian, Fliegauf, Maximilian, Bosch, Lance Fredrick Pahutan, Ulupinar, Hatice, Hagemeyer, Nora, Schreiner, Dietmar, Dorrier, Cayce, Tsuda, Makoto, Grothe, Claudia, Joutel, Anne, Daneman, Richard, Betsholtz, Christer, Lendahl, Urban, Knobeloch, Klaus-Peter, Lmmermann, Tim, Priller, Josef, Kierdorf, Katrin, Prinz, Marco

Issue&Volume: 2022-04-20

Abstract: All tissue-resident macrophages of the central nervous system (CNS)—including parenchymal microglia, as well as CNS-associated macrophages (CAMs1) such as meningeal and perivascular macrophages2,3,4,5,6,7—are part of the CNS endogenous innate immune system that acts as the first line of defence during infections or trauma2,8,9,10. It has been suggested that microglia and all subsets of CAMs are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors11,12,13,14,15. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAM subsets in situ are poorly understood. Here we show, using fate-mapping systems, single-cell profiling and cell-specific mutants, that only meningeal macrophages and microglia share a common prenatal progenitor. By contrast, perivascular macrophages originate from perinatal meningeal macrophages only after birth in an integrin-dependent manner. The establishment of perivascular macrophages critically requires the presence of arterial vascular smooth muscle cells. Together, our data reveal a precisely timed process in distinct anatomical niches for the establishment of macrophage subsets in the CNS.

DOI: 10.1038/s41586-022-04596-2

Source: https://www.nature.com/articles/s41586-022-04596-2

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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