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一种新型小胶质细胞亚群在发育中的大脑髓鞘形成中起关键作用。

A novel microglial subset plays a key role in myelinogenesis in developing brain.

作者信息

Wlodarczyk Agnieszka, Holtman Inge R, Krueger Martin, Yogev Nir, Bruttger Julia, Khorooshi Reza, Benmamar-Badel Anouk, de Boer-Bergsma Jelkje J, Martin Nellie A, Karram Khalad, Kramer Isabella, Boddeke Erik Wgm, Waisman Ari, Eggen Bart Jl, Owens Trevor

机构信息

Department of Neurobiology Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Department of Neuroscience, Medical Physiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

出版信息

EMBO J. 2017 Nov 15;36(22):3292-3308. doi: 10.15252/embj.201696056. Epub 2017 Sep 28.

Abstract

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin-like growth factor 1, and its selective depletion from CD11c microglia leads to impairment of primary myelination. CD11c-targeted toxin regimens induced a selective transcriptional response in neonates, distinct from adult microglia. CD11c microglia are also found in clusters of repopulating microglia after experimental ablation and in neuroinflammation in adult mice, but despite some similarities, they do not recapitulate neonatal microglial characteristics. We therefore identify a unique phenotype of neonatal microglia that deliver signals necessary for myelination and neurogenesis.

摘要

小胶质细胞是中枢神经系统中的常驻巨噬细胞,有助于维持体内平衡和神经炎症。尽管已知其在大脑发育中起重要作用,但其确切功能尚未完全阐明。在这里,我们表明,与健康的成年细胞和炎症激活细胞不同,新生小胶质细胞表现出独特的成髓鞘和神经发生表型。在发育中大脑的主要髓鞘形成区域占主导地位的CD11c小胶质细胞亚群表达神经元和神经胶质细胞存活、迁移及分化相关基因。这些细胞是胰岛素样生长因子1的主要来源,从CD11c小胶质细胞中选择性去除该因子会导致原发性髓鞘形成受损。靶向CD11c的毒素方案在新生儿中诱导了一种与成年小胶质细胞不同的选择性转录反应。在实验性消融后重新填充的小胶质细胞簇以及成年小鼠的神经炎症中也发现了CD11c小胶质细胞,但尽管存在一些相似之处,它们并未重现新生小胶质细胞的特征。因此,我们确定了新生小胶质细胞的一种独特表型,该表型传递髓鞘形成和神经发生所需的信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7421/5686552/7252727ee52d/EMBJ-36-3292-g002.jpg

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