Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration

被引：286

作者：

O'Koren, Emily G. ^{[1
]}

Yu, Chen ^{[1
]}

Klingeborn, Mikael ^{[1
]}

Wong, Alicia Y. W. ^{[2
]}

Prigge, Cameron L. ^{[3
]}

Mathew, Rose ^{[1
]}

Kalnitsky, Joan ^{[1
]}

Msallam, Rasha A. ^{[2
]}

Silvin, Aymeric ^{[2
]}

Kay, Jeremy N. ^{[1
,3
]}

Rickman, Catherine Bowes ^{[1
,5
]}

Arshavsky, Vadim Y. ^{[1
,4
]}

Ginhoux, Florent ^{[2
]}

Merad, Miriam ^{[6
,7
]}

Saban, Daniel R. ^{[1
,8
]}

机构：

[1] Duke Univ, Dept Ophthalmol, Durham, NC 27710 USA

[2] ASTAR, Singapore Immunol Network SIgN, Singapore 138648, Singapore

[3] Duke Univ, Dept Neurobiol, Durham, NC 27710 USA

[4] Duke Univ, Dept Pharmacol, Durham, NC 27710 USA

[5] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA

[6] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[8] Duke Univ, Dept Immunol, Durham, NC 27710 USA

来源：

IMMUNITY | 2019年 / 50卷 / 03期

关键词：

GENE-EXPRESSION SIGNATURE; MACULAR DEGENERATION; RETINITIS-PIGMENTOSA; ACTIVATED MICROGLIA; LANGERHANS CELLS; ADULT MICROGLIA; GANGLION-CELL; MOUSE; MAINTENANCE; REGION;

D O I：

10.1016/j.immuni.2019.02.007

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Microglia from different nervous system regions are molecularly and anatomically distinct, but whether they also have different functions is unknown. We combined lineage tracing, single-cell transcriptomics, and electrophysiology of the mouse retina and showed that adult retinal microglia shared a common developmental lineage and were long-lived but resided in two distinct niches. Microglia in these niches differed in their interleukin-34 dependency and functional contribution to visual-information processing. During certain retinal-degeneration models, microglia from both pools relocated to the subretinal space, an inducible disease-associated niche that was poorly accessible to monocyte-derived cells. This microglial transition involved transcriptional reprogramming of microglia, characterized by reduced expression of homeostatic checkpoint genes and upregulation of injury-responsive genes. This transition was associated with protection of the retinal pigmented epithelium from damage caused by disease. Together, our data demonstrate that microglial function varies by retinal niche, thereby shedding light on the significance of microglia heterogeneity.

引用

页码：723 / +

页数：22

共 71 条

[1] Local self-renewal can sustain CNS microglia maintenance and function throughout adult life [J].

Ajami, Bahareh ;

Bennett, Jami L. ;

Krieger, Charles ;

Tetzlaff, Wolfram ;

Rossi, Fabio M. V. .

NATURE NEUROSCIENCE, 2007, 10 (12) :1538-1543

[2] New tools for studying microglia in the mouse and human CNS [J].

Bennett, Mariko L. ;

Bennett, F. Chris ;

Liddelow, Shane A. ;

Ajami, Bahareh ;

Zamanian, Jennifer L. ;

Fernhoff, Nathaniel B. ;

Mulinyawe, Sara B. ;

Bohlen, Christopher J. ;

Adil, Aykezar ;

Tucker, Andrew ;

Weissman, Irving L. ;

Chang, Edward F. ;

Li, Gordon ;

Grant, Gerald A. ;

Gephart, Melanie G. Hayden ;

Barres, Ben A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (12) :E1738-E1746

[3] LINKAGE MAPPING OF AUTOSOMAL DOMINANT RETINITIS-PIGMENTOSA (RP1) TO THE PERICENTRIC REGION OF HUMAN CHROMOSOME-8 [J].

BLANTON, SH ;

HECKENLIVELY, JR ;

COTTINGHAM, AW ;

FRIEDMAN, J ;

SADLER, LA ;

WAGNER, M ;

FRIEDMAN, LH ;

DAIGER, SP .

GENOMICS, 1991, 11 (04) :857-869

[4]

Brown NL, 2001, DEVELOPMENT, V128, P2497

[5] A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration [J].

Buch, T ;

Heppner, FL ;

Tertilt, C ;

Heinen, TJAJ ;

Kremer, M ;

Wunderlich, FT ;

Jung, S ;

Waisman, A .

NATURE METHODS, 2005, 2 (06) :419-426

[6] Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].

Butler, Andrew ;

Hoffman, Paul ;

Smibert, Peter ;

Papalexi, Efthymia ;

Satija, Rahul .

NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+

[7] Identification of a unique TGF-β dependent molecular and functional signature in microglia [J].

Butovsky, Oleg ;

Jedrychowski, Mark P. ;

Moore, Craig S. ;

Cialic, Ron ;

Lanser, Amanda J. ;

Gabriely, Galina ;

Koeglsperger, Thomas ;

Dake, Ben ;

Wu, Pauline M. ;

Doykan, Camille E. ;

Fanek, Zain ;

Liu, LiPing ;

Chen, Zhuoxun ;

Rothstein, Jeffrey D. ;

Ransohoffl, Richard M. ;

Gygi, Steven P. ;

Antel, Jack P. ;

Weiner, Howard L. .

NATURE NEUROSCIENCE, 2014, 17 (01) :131-143

[8] Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation [J].

Calippe, Bertrand ;

Augustin, Sebastien ;

Beguier, Fanny ;

Charles-Messance, Hugo ;

Poupel, Lucie ;

Conart, Jean-Baptiste ;

Hu, Shulong J. ;

Lavalette, Sophie ;

Fauvet, Alexandre ;

Rayes, Julie ;

Levy, Olivier ;

Raoul, William ;

Fitting, Catherine ;

Denefle, Thomas ;

Pickering, Matthew C. ;

Harris, Claire ;

Jorieux, Sylvie ;

Sullivan, Patrick M. ;

Sahel, Jose -Alain ;

Karoyan, Philippe ;

Sapieha, Przemyslaw ;

Guillonneau, Xavier ;

Gautier, Emmanuel L. ;

Sennlaub, Florian .

IMMUNITY, 2017, 46 (02) :261-272

[9] 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

[10] A strong and highly significant QTL on chromosome 6 that protects the mouse from age-related retinal degeneration [J].

Danciger, M ;

Lyon, J ;

Worrill, D ;

LaVail, MM ;

Yang, HD .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2003, 44 (06) :2442-2449

← 1 2 3 4 5 6 7 8 →