Cx3cr1-deficient microglia exhibit a premature aging transcriptome

被引：63

作者：

Gyoneva, Stefka ^{[1
]}

Hosur, Raghavendra ^{[2
]}

Gosselin, David ^{[3
,6
]}

Zhang, Baohong ^{[2
]}

Ouyang, Zhengyu ^{[3
]}

Cotleur, Anne C. ^{[1
]}

Peterson, Michael ^{[4
]}

Allaire, Norm ^{[2
]}

Challa, Ravi ^{[2
]}

Cullen, Patrick ^{[2
]}

Roberts, Chris ^{[2
]}

Miao, Kelly ^{[1
]}

Reynolds, Taylor L. ^{[4
]}

Glass, Christopher K. ^{[3
,5
]}

Burkly, Linda ^{[1
]}

Ransohoff, Richard M. ^{[1
,7
]}

机构：

[1] Biogen, Acute Neurol, Cambridge, MA 02142 USA

[2] Biogen, Computat Biol & Genom, Cambridge, MA USA

[3] Univ Calif San Diego, Cell & Mol Med, San Diego, CA 92103 USA

[4] Biogen, Translat Neuropathol, Cambridge, MA USA

[5] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA

[6] Univ Laval, Fac Med, CHU Quebec Res Ctr, Dept Mol Med, Quebec City, PQ, Canada

[7] Harvard Med Sch, Dept Cell Biol, Cambridge, MA 02139 USA

来源：

LIFE SCIENCE ALLIANCE | 2019年 / 2卷 / 06期

关键词：

AMYLOID DEPOSITION; ALZHEIMERS-DISEASE; DEFICIENCY LEADS; FRACTALKINE; CX3CR1; ACTIVATION; ADULT; MATURATION; ENVIRONMENT; MACROPHAGE;

D O I：

10.26508/lsa.201900453

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA-sequencing (RNA-seq). In 2-mo-old mice, Cx3cr1 deletion resulted in the down-regulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a comparable fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1-deficient mice useful for studying aged microglia.

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页数：16

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共 61 条

[1] Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth [J].

Araki, T ;

Milbrandt, J .

NEURON, 1996, 17 (02) :353-361

[2] Epigenetic regulation of brain region-specific microglia clearance activity [J].

Ayata, Pinar ;

Badimon, Ana ;

Strasburger, Hayley J. ;

Duff, Mary Kaye ;

Montgomery, Sarah E. ;

Loh, Yong-Hwee E. ;

Ebert, Anja ;

Pimenova, Anna A. ;

Ramirez, Brianna R. ;

Chan, Andrew T. ;

Sullivan, Josefa M. ;

Purushothaman, Immanuel ;

Scarpa, Joseph R. ;

Goate, Alison M. ;

Busslinger, Meinrad ;

Shen, Li ;

Losic, Bojan ;

Schaefer, Anne .

NATURE NEUROSCIENCE, 2018, 21 (08) :1049-+

[3] Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats [J].

Bachstetter, Adam D. ;

Morganti, Josh M. ;

Jernberg, Jennifer ;

Schlunk, Andrea ;

Mitchell, Staten H. ;

Brewster, Kaelin W. ;

Hudson, Charles E. ;

Cole, Michael J. ;

Harrison, Jeffrey K. ;

Bickford, Paula C. ;

Gemma, Carmelina .

NEUROBIOLOGY OF AGING, 2011, 32 (11) :2030-2044

[4] 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-+

[5] Regulation of Tau Pathology by the Microglial Fractalkine Receptor [J].

Bhaskar, Kiran ;

Konerth, Megan ;

Kokiko-Cochran, Olga N. ;

Cardona, Astrid ;

Ransohoff, Richard M. ;

Lamb, Bruce T. .

NEURON, 2010, 68 (01) :19-31

[6] Absence of microglial CX3CR1 impairs the synaptic integration of adult-born hippocampal granule neurons [J].

Bolos, M. ;

Perea, J. R. ;

Terreros-Roncal, J. ;

Pallas-Bazarra, N. ;

Jurado-Arjona, J. ;

Avila, J. ;

Llorens-Martin, M. .

BRAIN BEHAVIOR AND IMMUNITY, 2018, 68 :76-89

[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] Sall1 is a transcriptional regulator defining microglia identity and function [J].

Buttgereit, Anne ;

Lelios, Iva ;

Yu, Xueyang ;

Vrohlings, Melissa ;

Krakoski, Natalie R. ;

Gautier, Emmanuel L. ;

Nishinakamura, Ryuichi ;

Becher, Burkhard ;

Greter, Melanie .

NATURE IMMUNOLOGY, 2016, 17 (12) :1397-1406

[9] Control of microglial neurotoxicity by the fractalkine receptor [J].

Cardona, Astrid E. ;

Pioro, Erik P. ;

Sasse, Margaret E. ;

Kostenko, Volodymyr ;

Cardona, Sandra M. ;

Dijkstra, Ineke M. ;

Huang, DeRen ;

Kidd, Grahame ;

Dombrowski, Stephen ;

Dutta, RanJan ;

Lee, Jar-Chi ;

Cook, Donald N. ;

Jung, Steffen ;

Lira, Sergio A. ;

Littman, Dan R. ;

Ransohoff, Richard M. .

NATURE NEUROSCIENCE, 2006, 9 (07) :917-924

[10] Microglia: Multitasking Specialists of the Brain [J].

Casano, Alessandra Maria ;

Peri, Francesca .

DEVELOPMENTAL CELL, 2015, 32 (04) :469-477

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