<i>Cx3cr1-</i>deficient microglia exhibit a premature aging transcriptome

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 <i>Cx3cr1</i> signaling are not well understood. Here, we analyzed transcriptomes of <i>Cx3cr1-</i>deficient microglia under varying conditions by RNA-sequencing (RNA-seq). In 2-mo-old mice, <i>Cx3cr1</i> deletion resulted in the down-regulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, <i>Cx3cr1-</i>deficient microglia from young mice exhibited a transcriptome consistent with that of aged <i>Cx3cr1-</i>sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of <i>Cx3cr1</i> 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 <i>Cx3cr1</i>-deficient mice useful for studying aged microglia.