Cross-species analysis across 450 million years of evolution reveals conservation and divergence of the microglia program (bulk RNA-seq)

Here we characterize microglia transcriptional program across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to human, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, while humans express significant microglia heterogeneity. In addition, we observed notable differences in complement, phagocytic and several critical signaling pathways that are enriched with susceptibility genes to brain disorders, including Alzheimer’s and Parkinson’s disease in microglia of common animal models as compared to human. Our study provides an essential resource of conserved and divergent microglia pathways across evolution with important implications for future development of microglia-based therapies in humans. Single cell and bulk RNA-seq of microglia from 10 different species and comparison of transcriptional landcape over species. Biological replicates of different species were n=3-6. The raw data for human subjects will be submitted through EGA for controlled access.