A new fate mapping system reveals context-dependent random or clonal expansion of microglia

被引：421

作者：

Tay, Tuan Leng ^{[1
]}

Mai, Dominic ^{[2
]}

Dautzenberg, Jana ^{[1
]}

Fernandez-Klett, Francisco ^{[3
,4
]}

Lin, Gen ^{[5
]}

Sagar ^{[6
]}

Datta, Moumita ^{[1
]}

Drougard, Anne ^{[6
]}

Stempfl, Thomas ^{[7
]}

Ardura-Fabregat, Alberto ^{[1
]}

Staszewski, Ori ^{[1
]}

Margineanu, Anca ^{[8
]}

Sporbert, Anje ^{[8
]}

Steinmetz, Lars M. ^{[5
,9
,10
]}

Pospisilik, J. Andrew

Jung, Steffen ^{[11
]}

Priller, Josef ^{[3
,4
,12
,13
]}

Gruen, Dominic ^{[6
]}

Ronneberger, Olaf ^{[2
]}

Prinz, Marco ^{[1
,14
]}

机构：

[1] Univ Freiburg, Inst Neuropathol, Fac Med, Freiburg, Germany

[2] Univ Freiburg, Inst Comp Sci, Freiburg, Germany

[3] Charite, Dept Neuropsychiat, Berlin, Germany

[4] Charite, Lab Mol Psychiat, Berlin, Germany

[5] European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany

[6] Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany

[7] Univ Regensburg, Ctr Excellence Fluorescent Bioanalyt, Regensburg, Germany

[8] Max Delbruck Ctr Mol Med, Adv Light Microscopy Technol Platform, Berlin, Germany

[9] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[10] Stanford Genome Technol Ctr, Palo Alto, CA USA

[11] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[12] German Ctr Neurodegenerat Dis DZNE, Cluster Excellence NeuroCure, Berlin, Germany

[13] BIH, Berlin, Germany

[14] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Freiburg, Germany

来源：

NATURE NEUROSCIENCE | 2017年 / 20卷 / 06期

关键词：

RESIDENT MICROGLIA; ADULT MICROGLIA; YOLK-SAC; IN-VIVO; MACROPHAGES; PROLIFERATION; INFLAMMATION; RESOLUTION; MONOCYTES; CELLS;

D O I：

10.1038/nn.4547

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Microglia constitute a highly specialized network of tissue-resident immune cells that is important for the control of tissue homeostasis and the resolution of diseases of the CNS. Little is known about how their spatial distribution is established and maintained in vivo. Here we establish a new multicolor fluorescence fate mapping system to monitor microglial dynamics during steady state and disease. Our findings suggest that microglia establish a dense network with regional differences, and the high regional turnover rates found challenge the universal concept of microglial longevity. Microglial self-renewal under steady state conditions constitutes a stochastic process. During pathology this randomness shifts to selected clonal microglial expansion. In the resolution phase, excess disease-associated microglia are removed by a dual mechanism of cell egress and apoptosis to re-establish the stable microglial network. This study unravels the dynamic yet discrete self-organization of mature microglia in the healthy and diseased CNS.

引用

页码：793 / +

页数：14

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