Transcriptome sequencing elucidates gene modules in microglia

Microglia are multifunctional cells that are important for brain development and homeostasis. Despite the growing evidence of their complexity, the field lacks a unified system for categorizing the many microglial states. In an effort to develop a comprehensive classification system, we profiled transcriptomes of mouse microglia in 96 different stimulus conditions. We generated fine-resolution gene modules that are robustly preserved across datasets by employing a two-step clustering approach. These modules served as the basis for a combinatorial code that we then used to characterize microglial activation under inflammatory stimulus conditions in vitro. Many of the modules were preserved in vivo, and were differentially regulated during acute inflammation and in aging. In summary, the microglial gene modules presented here are a novel resource for classifying and characterizing microglial states in health and disease. Transcriptome profiles from microglia activated in 96 different stimulus conditions in vitro and 2 conditions in vivo. Each condition had a minimum of 3 replicates, for a total of 922 samples.