A transcriptomic microglia taxonomy across mouse and human pathologies

Area of Science:

• Neuroscience
• Immunology
• Genomics

Background:

• Single-cell studies highlight significant microglial diversity in brain development, homeostasis, and disease.
• A unified framework is essential for comparing and stratifying microglial states across various contexts.

Purpose of the Study:

• To generate a comprehensive atlas of myeloid cell states in the central nervous system (CNS).
• To establish a taxonomy for stratifying microglial states across physiological and pathological conditions.
• To map the spatial organization and interactions of CNS immune cells.

Main Methods:

• Single-cell RNA sequencing of over one million CNS cells from more than 30 conditions.
• Spatial transcriptomics to map immune cell states within tissue microenvironments.
• In vivo perturbations to investigate signaling pathways regulating microglial states.

Main Results:

• Developed a taxonomy of 27 superclusters and 192 clusters of myeloid cell states, largely conserved across diseases.
• Mapped the spatial distribution and local interactions of immune cell states using spatial transcriptomics.
• Demonstrated that activation-associated microglial states depend on interferon and CSF1R signaling.

Conclusions:

• The study provides a spatially aware taxonomic framework for CNS immune cells in health and disease.
• This atlas enables a deeper understanding of microglial diversity and function across the lifespan and in various pathologies.
• The findings offer a foundation for future research into targeted immunotherapies for neurological disorders.