Microglial states revisited: from homeostasis to disease.

Microglia in the CNS show multidimensional, transcriptionally diverse state transitions across development, region, sex, age, genotype, and environment, replacing binary resting/activated or M1/M2 views.

• Why it matters: Binary microglial frameworks miss how states shift during brain development, homeostasis, and responses to perturbation, limiting understanding of interindividual differences in disease trajectories.
• What they did: Using advances in single-cell/single-nucleus transcriptomics, chromatin accessibility profiling, and spatial multi-omics, researchers map microglial sensome, homeostatic and disease-associated signatures, including latent programmes revealed by challenges.
• The result: The state-space model links transcriptomic transitions to neurodegeneration, demyelination, infection, and systemic inflammation, and supports translating state-resolved insights into biomarkers and interventions.

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