We profiled human central nervous system (CNS)-associated macrophages (CAMs) in anatomically dissected CNS interface tissue from typical, fetal and glioblastoma-affected brains using single-cell multi-omics and spatially resolved transcriptomic techniques. Analyses of CAM (and microglia) turnover rates in stem-cell-transplanted glioblastoma and prenatal tissues highlighted the developmental phenotypes of these cells in patients, which lays the groundwork for potential replacement therapies.
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References
Masuda, T. et al. Specification of CNS macrophage subsets occurs postnatally in defined niches. Nature 604, 740–748 (2022). This paper reports the common origin of CAMs and microglia and the postnatal maturation of the brain perivascular space in mice.
Goldmann, T. et al. Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat. Immunol. 17, 797–805 (2016). This study shows that CAMs, like microglia, are long-lived yolk-sac-derived cells and are largely derived from prenatal sources.
Jordão, M. J. C. et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 363, eaat7554 (2019). This paper reports that CAMs and demyelination-associated macrophages show broad transcriptional overlaps.
Prinz, M., Masuda, T., Wheeler, M. A. & Quintana, F. J. Microglia and central nervous system–associated macrophages — from origin to disease modulation. Annu. Rev. Immunol. 39, 251–277 (2021). This review article discusses the pathological and physiological functions of CAMs.
Sankowski, R. et al. Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease. EMBO J. 40, e108605 (2021). This paper reports that CAMs are functionally influenced by systemically occurring microbiota metabolites.
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This is a summary of: Sankowski, R. et al. Multiomic spatial landscape of innate immune cells at human central nervous system borders. Nat. Med. https://doi.org/10.1038/s41591-023-02673-1 (2023).
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Human CNS-associated macrophages decoded in time and space. Nat Med 30, 49–50 (2024). https://doi.org/10.1038/s41591-023-02750-5
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DOI: https://doi.org/10.1038/s41591-023-02750-5
