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A transcriptomic microglia taxonomy across mouse and human pathologies.

Chintan Chhatbar1, Roman Sankowski1,2, Michael Schulz1

  • 1Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.

Nature Immunology
|March 26, 2026
PubMed
Summary
This summary is machine-generated.

Researchers created a comprehensive atlas of over one million central nervous system cells, revealing a conserved taxonomy of myeloid cell states across diverse brain conditions. This framework aids in understanding immune cell roles in health and disease.

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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.