The transcriptional landscape of human microglia reveals strong conservation of miRNAs and preservation of function across vertebrate species.

The central role of microglia in CNS function in health and disease has resulted in large interest in targeting microglial as treatments for neurodegenerative disease; understanding the factors that regulate microglial gene expression will be crucial to this goal. microRNAs (miRNAs) are among the most abundant post transcriptional regulators of gene expression. miRNAs suggests miRNA were likely key to significant evolutionary events as regulators of gene expression. The miRNAome of microglia is critical to their correct functioning but the miRNA that define microglia identity and regulate key functions have not been fully defined. In this study we performed a detailed analysis of the microglial miRNAome to identify miRNA enriched in microglia that are conserved across species (human, mouse, and xenopus). We further characterised the expression of these conserved miRNAs during demyelination and remyelination and identified conserved function of a microglial-enriched miRNA across species. These findings reveal evolutionary conservation of specific miRNAs, suggesting an important role in establishing and maintaining microglial identity. They also highlight miRNAs that may be critical for microglial function in the central nervous system in both health and disease. Overall, this work advances our understanding of the factors that regulate microglial gene expression.