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