Gene expression profiles of M1 and M2 microglia characterized by comparative analysis of public datasets

Abstract

AbstractObjectiveMicroglia, immunocompetent cells in the central nervous system, adopt two distinct activation phenotypes, composed of a pro‐inflammatory and neurotoxic “classical” activation (M1) phenotype by exposure to lipopolysaccharide and interferon‐γ, and an anti‐inflammatory and neuroprotective “alternative” activation (M2) phenotype after treatment with interleukin‐4 and interleukin‐13. Recently, gene expression profiling using DNA microarray and high‐throughput sequencing technologies identified valid markers specific for microglia. However, we have fairly limited knowledge on comprehensive gene expression signatures of functionally polarized microglia. By comparative analysis of public datasets, we attempted to characterize the set of the genes specific for microglia polarized to M1, M2a and Mtgf, and the overlap of these marker genes in distinct activation phenotypes.MethodsWe retrieved five different microarray datasets of microglial gene expression from Gene Expression Omnibus, and analyzed them by GEO2R. We identified overlapping genes in various experimental conditions by Gene List Venn Diagram.ResultsWe found that the set of M1, M2a and Mtgf marker genes are highly variable among distinct datasets analyzed. Human microglia showed gene expression profiles quite different from those of mouse microglia. Rat amoeboid microglia in part showed the M1‐polarized phenotype. A substantial number of the genes upregulated under both M1‐polarizing and M2a‐polarizing conditions suggest common signaling pathways for M1 and M2 activation of microglia. Counteracting regulation was found between M1 and Mtgf gene expression.ConclusionsThe great variability of M1 and M2 microglial gene expression profiles is attributable to differences in the methods of preparation of microglia, culture conditions and platforms of microarray analyzed.