Cx3cr1-deficient microglia exhibit a premature aging transcriptome-Reference-Cited by-同舟云学术

Cx3cr1-deficient microglia exhibit a premature aging transcriptome

Published:2019-12 Issue:6 Volume:2 Page:e201900453
ISSN:2575-1077
Container-title:Life Science Alliance
language:en
Short-container-title:Life Sci. Alliance

Author:

Gyoneva Stefka¹^ORCID,Hosur Raghavendra²,Gosselin David³,Zhang Baohong²,Ouyang Zhengyu³,Cotleur Anne C¹^ORCID,Peterson Michael⁴^ORCID,Allaire Norm²,Challa Ravi²,Cullen Patrick²,Roberts Chris²,Miao Kelly¹,Reynolds Taylor L⁴,Glass Christopher K³⁵^ORCID,Burkly Linda¹,Ransohoff Richard M¹^ORCID

Affiliation:

1. Acute Neurology, Biogen, Cambridge, MA, USA

2. Computational Biology and Genomics, Biogen, Cambridge, MA, USA

3. Cell and Molecular Medicine, University of California San Diego, San Diego, CA, USA

4. Translational Neuropathology, Biogen, Cambridge, MA, USA

5. School of Medicine, University of California San Diego, San Diego, CA, USA

Abstract

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.

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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