Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program

被引：299

作者：

Geirsdottir, Laufey ^{[1
]}

David, Eyal ^{[1
]}

Keren-Shaul, Hadas ^{[1
,2
]}

Weiner, Assaf ^{[1
]}

Bohlen, Stefan Cornelius ^{[3
]}

Neuber, Jana ^{[3
]}

Balic, Adam ^{[4
,5
]}

Giladi, Amir ^{[1
]}

Sheban, Fadi ^{[1
]}

Dutertre, Charles-Antoine ^{[6
,7
]}

Pfeifle, Christine ^{[8
]}

Peri, Francesca ^{[9
]}

Raffo-Romero, Antonella ^{[10
]}

Vizioli, Jacopo ^{[10
]}

Matiasek, Kaspar ^{[11
]}

Scheiwe, Christian ^{[12
]}

Meckel, Stephan ^{[13
]}

Maetz-Rensing, Kerstin ^{[14
]}

van der Meer, Franziska ^{[14
]}

Thormodsson, Finnbogi Rutur ^{[15
]}

Stadelmann, Christine ^{[16
]}

Zilkha, Noga ^{[17
]}

Kimchi, Tali ^{[17
]}

Ginhoux, Florent ^{[6
,18
,19
]}

Ulitsky, Igor ^{[20
]}

Erny, Daniel ^{[3
,21
]}

Amit, Ido ^{[1
]}

Prinz, Marco ^{[3
,22
,23
,24
]}

机构：

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

[2] Weizmann Inst Sci, Life Sci Core Facil, Israel Natl Ctr Personalized Med G INCPM, Rehovot, Israel

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

[4] Univ Edinburgh, Roslin Inst, Easter Bush EH25 9RG, Scotland

[5] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush EH25 9RG, Scotland

[6] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore

[7] Duke NUS Med Sch, Program Emerging Infect Dis, 8 Coll Rd, Singapore, Singapore

[8] Max Planck Inst Evolutionary Biol, Dept Evolutionary Genet, Plon, Germany

[9] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland

[10] Univ Lille, INSERM, U1192, Lab Prote Reponse Inflammatoire & Spectrometrie M, Lille, France

[11] Ludwig Maximilians Univ Munchen, Ctr Clin Vet Med, Sect Clin & Comparat Neuropathol, Munich, Germany

[12] Univ Freiburg, Fac Med, Clin Neurosurg, Freiburg, Germany

[13] Univ Freiburg, Fac Med, Med Ctr, Dept Neuroradiol, Freiburg, Germany

[14] Leibniz Inst Primate Res, German Primate Ctr, Gottingen, Germany

[15] Innovat Ctr Iceland, Reykjavik, Iceland

[16] Univ Med Ctr Gottingen, Inst Neuropathol, Gottingen, Germany

[17] Weizmann Inst Sci, Dept Neurobiol, Rehovot, Israel

[18] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Sch Med, Shanghai, Peoples R China

[19] Singhlth Duke NUS Acad Med Ctr, Translat Immunol Inst, Singapore, Singapore

[20] Weizmann Inst Sci, Dept Biol Regulat, Rehovot, Israel

[21] Univ Freiburg, Fac Med, Berta Ottenstein Programme, Freiburg, Germany

[22] Univ Freiburg, Signaling Res Centres BIOSS, Freiburg, Germany

[23] Univ Freiburg, CIBSS, Freiburg, Germany

[24] Univ Freiburg, Fac Med, Ctr NeuroModulat, Freiburg, Germany

来源：

CELL | 2019年 / 179卷 / 07期

基金：

欧洲研究理事会; 英国生物技术与生命科学研究理事会; 新加坡国家研究基金会;

关键词：

CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; ADULT MICROGLIA; YOLK-SAC; MACROPHAGES; MOUSE; SENESCENCE; MONOCYTES; HEALTH; CD45;

D O I：

10.1016/j.cell.2019.11.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.

引用

页码：1609 / +

页数：30

共 89 条

[1] Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool [J].

Ajami, Bahareh ;

Bennett, Jami L. ;

Krieger, Charles ;

McNagny, Kelly M. ;

Rossi, Fabio M. V. .

NATURE NEUROSCIENCE, 2011, 14 (09) :1142-U263

[2] Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain [J].

Alliot, F ;

Godin, I ;

Pessac, B .

DEVELOPMENTAL BRAIN RESEARCH, 1999, 117 (02) :145-152

[3] Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain [J].

Askew, Katharine ;

Li, Kaizhen ;

Olmos-Alonso, Adrian ;

Garcia-Moreno, Fernando ;

Liang, Yajie ;

Richardson, Philippa ;

Tipton, Tom ;

Chapman, Mark A. ;

Riecken, Kristoffer ;

Beccari, Sol ;

Sierra, Amanda ;

Molnar, Zoltan ;

Cragg, Mark S. ;

Garaschuk, Olga ;

Perry, V. Hugh ;

Gomez-Nicola, Diego .

CELL REPORTS, 2017, 18 (02) :391-405

[4] Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17 [J].

Baker, Matt ;

Mackenzie, Ian R. ;

Pickering-Brown, Stuart M. ;

Gass, Jennifer ;

Rademakers, Rosa ;

Lindholm, Caroline ;

Snowden, Julie ;

Adamson, Jennifer ;

Sadovnick, A. Dessa ;

Rollinson, Sara ;

Cannon, Ashley ;

Dwosh, Emily ;

Neary, David ;

Melquist, Stacey ;

Richardson, Anna ;

Dickson, Dennis ;

Berger, Zdenek ;

Eriksen, Jason ;

Robinson, Todd ;

Zehr, Cynthia ;

Dickey, Chad A. ;

Crook, Richard ;

McGowan, Eileen ;

Mann, David ;

Boeve, Bradley ;

Feldman, Howard ;

Hutton, Mike .

NATURE, 2006, 442 (7105) :916-919

[5] Visualisation of chicken macrophages using transgenic reporter genes: insights into the development of the avian macrophage lineage [J].

Balic, Adam ;

Garcia-Morales, Carla ;

Vervelde, Lonneke ;

Gilhooley, Hazel ;

Sherman, Adrian ;

Garceau, Valerie ;

Gutowska, Maria W. ;

Burt, David W. ;

Kaiser, Pete ;

Hume, David A. ;

Sang, Helen M. .

DEVELOPMENT, 2014, 141 (16) :3255-3265

[6] MetaCell: analysis of single-cell RNA-seq data using K-nn graph partitions [J].

Baran, Yael ;

Bercovich, Akhiad ;

Sebe-Pedros, Arnau ;

Lubling, Yaniv ;

Giladi, Amir ;

Chomsky, Elad ;

Meir, Zohar ;

Hoichman, Michael ;

Lifshitz, Aviezer ;

Tanay, Amos .

GENOME BIOLOGY, 2019, 20 (01)

[7] A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure [J].

Baron, Maayan ;

Veres, Adrian ;

Wolock, Samuel L. ;

Faust, Aubrey L. ;

Gaujoux, Renaud ;

Vetere, Amedeo ;

Ryu, Jennifer Hyoje ;

Wagner, Bridget K. ;

Shen-Orr, Shai S. ;

Klein, Allon M. ;

Melton, Douglas A. ;

Yanai, Itai .

CELL SYSTEMS, 2016, 3 (04) :346-+

[8] A Combination of Ontogeny and CNS Environment Establishes Microglial Identity [J].

Bennett, F. Chris ;

Bennett, Mariko L. ;

Yaqoob, Fazeela ;

Mulinyawe, Sara B. ;

Grant, Gerald A. ;

Gephart, Melanie Hayden ;

Plowey, Edward D. ;

Barres, Ben A. .

NEURON, 2018, 98 (06) :1170-+

[9] VISTA expression by microglia decreases during inflammation and is differentially regulated in CNS diseases [J].

Borggrewe, Malte ;

Grit, Corien ;

Den Dunnen, Wilfred F. A. ;

Burm, Saskia M. ;

Bajramovic, Jeffrey J. ;

Noelle, Randolph J. ;

Eggen, Bart J. L. ;

Laman, Jon D. .

GLIA, 2018, 66 (12) :2645-2658

[10] The evolution of gene expression levels in mammalian organs [J].

Brawand, David ;

Soumillon, Magali ;

Necsulea, Anamaria ;

Julien, Philippe ;

Csardi, Gabor ;

Harrigan, Patrick ;

Weier, Manuela ;

Liechti, Angelica ;

Aximu-Petri, Ayinuer ;

Kircher, Martin ;

Albert, Frank W. ;

Zeller, Ulrich ;

Khaitovich, Philipp ;

Gruetzner, Frank ;

Bergmann, Sven ;

Nielsen, Rasmus ;

Paeaebo, Svante ;

Kaessmann, Henrik .

NATURE, 2011, 478 (7369) :343-+

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