A Combination of Ontogeny and CNS Environment Establishes Microglial Identity

被引：359

作者：

Bennett, F. Chris ^{[1
,2
]}

Bennett, Mariko L. ^{[1
]}

Yaqoob, Fazeela ^{[1
]}

Mulinyawe, Sara B. ^{[1
]}

Grant, Gerald A. ^{[3
]}

Gephart, Melanie Hayden ^{[3
]}

Plowey, Edward D. ^{[4
]}

Barres, Ben A. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

来源：

NEURON | 2018年 / 98卷 / 06期

关键词：

GENE-EXPRESSION; MONOCYTES; CELLS; REVEALS; MOUSE; MACROPHAGES; NEURODEGENERATION; TRANSCRIPTOME; MAINTENANCE; DISRUPTION;

D O I：

10.1016/j.neuron.2018.05.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Microglia, the brain's resident macrophages, are dynamic CNS custodians with surprising origins in the extra-embryonic yolk sac. The consequences of their distinct ontogeny are unknown but critical to understanding and treating brain diseases. We created a brain macrophage transplantation system to disentangle how environment and ontogeny specify microglial identity. We find that donor cells extensively engraft in the CNS of microglia-deficient mice, and even after exposure to a cell culture environment, microglia fully regain their identity when returned to the CNS. Though transplanted macrophages from multiple tissues can express microglial genes in the brain, only those of yolk-sac origin fully attain microglial identity. Transplanted macrophages of inappropriate origin, including primary human cells in a humanized host, express disease-associated genes and specific ontogeny markers. Through brain macrophage transplantation, we discover new principles of microglial identity that have broad applications to the study of disease and development of myeloid cell therapies.

引用

页码：1170 / +

页数：22

共 59 条

[11] A Neurodegeneration-Specific Gene-Expression Signature of Acutely Isolated Microglia from an Amyotrophic Lateral Sclerosis Mouse Model [J].

Chiu, Isaac M. ;

Morimoto, Emiko T. A. ;

Goodarzi, Hani ;

Liao, Jennifer T. ;

O'Keeffe, Sean ;

Phatnani, Hemali P. ;

Muratet, Michael ;

Carroll, Michael C. ;

Levy, Shawn ;

Tavazoie, Saeed ;

Myers, Richard M. ;

Maniatis, Tom .

CELL REPORTS, 2013, 4 (02) :385-401

[12] Normal aging induces A1-like astrocyte reactivity [J].

Clarke, Laura E. ;

Liddelow, Shane A. ;

Chakraborty, Chandrani ;

Munch, Alexandra E. ;

Heiman, Myriam ;

Barres, Ben A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (08) :E1896-E1905

[13]

Cronk J. C., 2018, J EXP MED, V215, P1

[14] Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects [J].

Dai, XM ;

Ryan, GR ;

Hapel, AJ ;

Dominguez, MG ;

Russell, RG ;

Kapp, S ;

Sylvestre, V ;

Stanley, ER .

BLOOD, 2002, 99 (01) :111-120

[15]

de Chaumont F, 2012, NAT METHODS, V9, P690, DOI [10.1038/NMETH.2075, 10.1038/nmeth.2075]

[16] The chemokine receptor CCR2 mediates the binding and internalization of monocyte chemoattractant protein-1 along brain microvessels [J].

Dzenko, KA ;

Andjelkovic, AV ;

Kuziel, WA ;

Pachter, JS .

JOURNAL OF NEUROSCIENCE, 2001, 21 (23) :9214-9223

[17] Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages [J].

Ginhoux, Florent ;

Greter, Melanie ;

Leboeuf, Marylene ;

Nandi, Sayan ;

See, Peter ;

Gokhan, Solen ;

Mehler, Mark F. ;

Conway, Simon J. ;

Ng, Lai Guan ;

Stanley, E. Richard ;

Samokhvalov, Igor M. ;

Merad, Miriam .

SCIENCE, 2010, 330 (6005) :841-845

[18] An environment-dependent transcriptional network specifies human microglia identity [J].

Gosselin, David ;

Skola, Dylan ;

Coufal, Nicole G. ;

Holtman, Inge R. ;

Schlachetzki, Johannes C. M. ;

Sajti, Eniko ;

Jaeger, Baptiste N. ;

O'Connor, Carolyn ;

Fitzpatrick, Conor ;

Pasillas, Martina P. ;

Pena, Monique ;

Adair, Amy ;

Gonda, David D. ;

Levy, Michael L. ;

Ransohoff, Richard M. ;

Gage, Fred H. ;

Glass, Christopher K. .

SCIENCE, 2017, 356 (6344) :1248-1259

[19] Environment Drives Selection and Function of Enhancers Controlling Tissue-Specific Macrophage Identities [J].

Gosselin, David ;

Link, Verena M. ;

Romanoski, Casey E. ;

Fonseca, Gregory J. ;

Eichenfield, Dawn Z. ;

Spann, Nathanael J. ;

Stender, Joshua D. ;

Chun, Hyun B. ;

Garner, Hannah ;

Geissmann, Frederic ;

Glass, Christopher K. .

CELL, 2014, 159 (06) :1327-1340

[20] Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation [J].

Hagemeyer, Nora ;

Kierdorf, Katrin ;

Frenzel, Kathrin ;

Xue, Jia ;

Ringelhan, Marc ;

Abdullah, Zeinab ;

Godin, Isabelle ;

Wieghofer, Peter ;

Jordao, Marta Joana Costa ;

Ulas, Thomas ;

Yorgancioglu, Guelden ;

Rosenbauer, Frank ;

Knolle, Percy A. ;

Heikenwalder, Mathias ;

Schultze, Joachim L. ;

Prinz, Marco .

EMBO JOURNAL, 2016, 35 (16) :1730-1744

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