Investigating Microglia in Health and Disease: Challenges and Opportunities

Microglia are tissue-resident macrophages implicated in central nervous system (CNS) development, homeostasis, and response to injury. Recent advances in transcriptomics, multiplex protein expression analysis, and experimental depletion of microglia have cemented their importance. However, it is still unclear which models are best suited to investigate microglia and explore their function in human disease. Here, we discuss issues regarding off-targeting during experimental manipulation, and differences and similarities between human and rodent microglia. With new developments in transgenic lines and human–rodent chimeras, we anticipate that in coming years, a clearer picture of microglia function in health and disease will emerge.