A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment

被引：713

作者：

Van Hove, Hannah ^{[1
,2
]}

Martens, Liesbet ^{[3
,4
]}

Scheyltjens, Isabelle ^{[1
,2
]}

De Vlaminck, Karen ^{[1
,2
]}

Antunes, Ana Rita Pombo ^{[1
,2
]}

De Prijck, Sofie ^{[4
,5
]}

Vandamme, Niels ^{[3
,4
,6
]}

De Schepper, Sebastiaan ^{[7
]}

Van Isterdael, Gert ^{[4
,8
]}

Scott, Charlotte L. ^{[4
,5
,9
]}

Aerts, Jeroen ^{[10
]}

Berx, Geert ^{[6
,11
]}

Boeckxstaene, Guy E. ^{[7
]}

Vandenbroucke, Roosmarijn E. ^{[4
,12
,13
]}

Vereecke, Lars ^{[13
,14
,15
]}

Moechars, Diederik ^{[10
]}

Guilliams, Martin ^{[4
,5
]}

Van Ginderachter, Jo A. ^{[1
,2
]}

Saeys, Yvan ^{[3
,16
]}

Movahedi, Kiavash ^{[1
,2
]}

机构：

[1] VIB Ctr Inflammat Res, Myeloid Cell Immunol Lab, Brussels, Belgium

[2] Vrije Univ Brussel, Lab Cellular & Mol Immunol, Brussels, Belgium

[3] VIB Ctr Inflammat Res, Data Min & Modeling Biomed, Ghent, Belgium

[4] Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium

[5] VIB Ctr Inflammat Res, Lab Myeloid Cell Ontogeny & Funct Specializat, Ghent, Belgium

[6] Canc Res Inst Ghent, Ghent, Belgium

[7] Katholieke Univ Leuven, Ctr Intestinal Neuroimmune Interact, Translat Res Ctr Gastrointestinal Disorders, Dept Chron Dis Metab & Ageing, Leuven, Belgium

[8] VIB Ctr Inflammat Res, VIB Flow Core, Ghent, Belgium

[9] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland

[10] Dept Neurosci Janssen Res & Dev, Beerse, Belgium

[11] Univ Ghent, Dept Biomed Mol Biol, Mol & Cellular Oncol Lab, Ghent, Belgium

[12] VIB Ctr Inflammat Res, Barriers Inflammat Lab, Ghent, Belgium

[13] Univ Ghent, Ghent Gut Inflammat Grp, Ghent, Belgium

[14] VIB Ctr Inflammat Res, Hostmicrobiota Interact Lab, Ghent, Belgium

[15] Univ Hosp Ghent, Dept Rheumatol, Ghent, Belgium

[16] Univ Ghent, Dept Appl Math Comp Sci & Stat, Ghent, Belgium

来源：

NATURE NEUROSCIENCE | 2019年 / 22卷 / 06期

关键词：

CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; DENDRITIC CELLS; MICROGLIA; DISEASE; IRF8; ORIGIN; PRECURSORS; CYTOSCAPE; MONOCYTES;

D O I：

10.1038/s41593-019-0393-4

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less well understood. By dissecting border regions and combining single-cell RNA-sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny, and subsets displayed distinct self-renewal capacity following depletion and repopulation. Single-cell and fate-mapping analysis both suggested that there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in both the healthy and diseased brain.

引用

页码：1021 / 1035

页数：15

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