Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry

被引：326

作者：

Boettcher, Chotima ^{[1
,2
]}

Schlickeiser, Stephan ^{[3
]}

Sneeboer, Marjolein A. M. ^{[4
]}

Kunkel, Desiree ^{[3
]}

Knop, Anniki ^{[1
,2
]}

Paza, Evdokia ^{[1
,2
]}

Fidzinski, Pawel ^{[5
]}

Kraus, Larissa ^{[5
,6
]}

Snijders, Gijsje J. L. ^{[4
]}

Kahn, Rene S. ^{[7
]}

Schulz, Axel R. ^{[8
]}

Mei, Henrik E. ^{[8
]}

Hol, Elly M. ^{[4
,10
]}

Siegmund, Britta ^{[11
]}

Glauben, Rainer ^{[11
]}

Spruth, Eike J. ^{[1
,2
,12
]}

de Witte, Lot D. ^{[4
,7
]}

Priller, Josef ^{[1
,2
,6
,12
,13
,14
,15
]}

机构：

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

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

[3] Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany

[4] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Utrecht, Netherlands

[5] Charite Univ Med Berlin, Epilepsy Ctr Berlin Brandenburg, Dept Neurol, Berlin, Germany

[6] Berlin Inst Hlth, Berlin, Germany

[7] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[8] German Rheumatism Res Ctr, Berlin, Germany

[9] Netherlands Brain Bank, Amsterdam, Netherlands

[10] Inst Royal Acad Arts & Sci, Netherlands Inst Neurosci, Dept Neuroimmunol, Amsterdam, Netherlands

[11] Charite Univ Med Berlin, Med Dept Gastroenterol, Div Gastroenterol Infectiol & Rheumatol, Berlin, Germany

[12] DZNE, Berlin, Germany

[13] Cluster Excellence NeuroCure, Berlin, Germany

[14] Univ Edinburgh, Edinburgh, Midlothian, Scotland

[15] UK Dementia Res Inst, Edinburgh, Midlothian, Scotland

来源：

NATURE NEUROSCIENCE | 2019年 / 22卷 / 01期

基金：

欧盟地平线“2020”;

关键词：

REVEALS; EXPRESSION; MACROPHAGES; RECEPTOR; DISCOVERY; SUBSETS; SYSTEM; MOUSE; AGE; HIV;

D O I：

10.1038/s41593-018-0290-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Microglia, the specialized innate immune cells of the CNS, play crucial roles in neural development and function. Different phenotypes and functions have been ascribed to rodent microglia, but little is known about human microglia (huMG) heterogeneity. Difficulties in procuring huMG and their susceptibility to cryopreservation damage have limited large-scale studies. Here we applied multiplexed mass cytometry for a comprehensive characterization of postmortem huMG (10(3) - 10(4) cells). We determined expression levels of 57 markers on huMG isolated from up to five different brain regions of nine donors. We identified the phenotypic signature of huMG, which was distinct from peripheral myeloid cells but was comparable to fresh huMG. We detected microglia regional heterogeneity using a hybrid workflow combining Cytobank and R/Bioconductor for multidimensional data analysis. Together, these methodologies allowed us to perform high-dimensional, large-scale immunophenotyping of huMG at the single-cell level, which facilitates their unambiguous profiling in health and disease.

引用

页码：78 / +

页数：19

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