Mapping microglia states in the human brain through the integration of high-dimensional techniques

被引：333

作者：

Sankowski, Roman ^{[1
,2
]}

Bottcher, Chotima ^{[3
,4
]}

Masuda, Takahiro ^{[1
]}

Geirsdottir, Laufey ^{[1
]}

Sagar ^{[5
]}

Sindram, Elena ^{[1
]}

Seredenina, Tamara ^{[6
]}

Muhs, Andreas ^{[6
]}

Scheiwe, Christian ^{[7
]}

Shah, Mukesch Johannes ^{[7
]}

Heiland, Dieter Henrik ^{[7
]}

Schnell, Oliver ^{[7
]}

Grun, Dominic ^{[5
,8
,9
]}

Priller, Josef ^{[3
,4
,10
,11
,12
,13
]}

Prinz, Marco ^{[1
,8
,9
,14
]}

机构：

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

[2] Univ Freiburg, Fac Med, Berta Ottenstein Programme Clinician Scientists, Freiburg, Germany

[3] Charite Univ Med Berlin, Dept Neuropsychiat, Berlin, Germany

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

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

[6] AC Immune, Lausanne, Switzerland

[7] Univ Freiburg, Dept Neurosurg, Fac Med, Freiburg, Germany

[8] Univ Freiburg, Signalling Res Ctr BIOSS, Freiburg, Germany

[9] Univ Freiburg, Signalling Res Ctr CIBSS, Freiburg, Germany

[10] DZNE, Berlin, Germany

[11] BIH, Berlin, Germany

[12] Univ Edinburgh, Edinburgh, Midlothian, Scotland

[13] UK DRI, Edinburgh, Midlothian, Scotland

[14] Univ Freiburg, Fac Med, Ctr Basics NeuroModulat NeuroModulBasics, Freiburg, Germany

来源：

NATURE NEUROSCIENCE | 2019年 / 22卷 / 12期

基金：

欧洲研究理事会;

关键词：

GENE-EXPRESSION; MYELOID CELLS; SINGLE; HETEROGENEITY; MACROPHAGES; DIVERSITY; FATE; AGE; MYELINOGENESIS; MAINTENANCE;

D O I：

10.1038/s41593-019-0532-y

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.

引用

页码：2098 / +

页数：26

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