Hagemeyer Nora, Hanft Klara-Maria, Akriditou Maria-Anna, Unger Nicole, Park Eun S, Stanley E Richard, Staszewski Ori, Dimou Leda, Prinz Marco
Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Molecular and Translational Neuroscience, Department of Neurology, Medical Faculty, Ulm University, Ulm, Germany.
Acta Neuropathol. 2017 Sep;134(3):441-458. doi: 10.1007/s00401-017-1747-1. Epub 2017 Jul 6.
Whereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the "fountain of microglia" that appears only postnatally in myelinated regions such as corpus callosum and cerebellum. Using large-scale transcriptional profiling, fate mapping, and genetic targeting approaches, we identified a unique molecular signature of this microglia subset that arose from a CNS endogenous microglia pool independent from circulating myeloid cells. Microglia depletion experiments revealed an essential role of postnatal microglia for the proper development and homeostasis of oligodendrocytes and their progenitors. Our data provide new cellular and molecular insights into the myelin-supporting function of microglia in the normal CNS.
虽然小胶质细胞参与几乎所有脑部疾病这一点已被广泛接受,但它们在中枢神经系统(CNS)稳态控制中的作用主要被认为是通过在发育中和成年大脑中形成、优化和监测突触来维持神经元功能。尽管最近已经阐明了皮质小胶质细胞的产前起源以及以神经元为中心的功能,但对于以前被描述为“小胶质细胞之源”的独特阿米巴样小胶质细胞群体却知之甚少,这种细胞仅在出生后出现在诸如胼胝体和小脑等有髓鞘区域。通过大规模转录谱分析、命运图谱绘制和基因靶向方法,我们确定了这个小胶质细胞亚群的独特分子特征,它源自中枢神经系统内源性小胶质细胞池,独立于循环髓样细胞。小胶质细胞耗竭实验揭示了出生后小胶质细胞对少突胶质细胞及其前体细胞的正常发育和稳态的重要作用。我们的数据为正常中枢神经系统中小胶质细胞的髓鞘支持功能提供了新的细胞和分子见解。