Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages

Natalia Ochocka, Pawel Segit, Kacper Adam Walentynowicz, Kamil Wojnicki, Salwador Cyranowski, Julian Swatler, Jakub Mieczkowski () and Bozena Kaminska ()
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Natalia Ochocka: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Pawel Segit: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Kacper Adam Walentynowicz: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Kamil Wojnicki: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Salwador Cyranowski: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Julian Swatler: Laboratory of Cytometry, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Jakub Mieczkowski: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Bozena Kaminska: Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Microglia are resident myeloid cells in the central nervous system (CNS) that control homeostasis and protect CNS from damage and infections. Microglia and peripheral myeloid cells accumulate and adapt tumor supporting roles in human glioblastomas that show prevalence in men. Cell heterogeneity and functional phenotypes of myeloid subpopulations in gliomas remain elusive. Here we show single-cell RNA sequencing (scRNA-seq) of CD11b+ myeloid cells in naïve and GL261 glioma-bearing mice that reveal distinct profiles of microglia, infiltrating monocytes/macrophages and CNS border-associated macrophages. We demonstrate an unforeseen molecular heterogeneity among myeloid cells in naïve and glioma-bearing brains, validate selected marker proteins and show distinct spatial distribution of identified subsets in experimental gliomas. We find higher expression of MHCII encoding genes in glioma-activated male microglia, which was corroborated in bulk and scRNA-seq data from human diffuse gliomas. Our data suggest that sex-specific gene expression in glioma-activated microglia may be relevant to the incidence and outcomes of glioma patients.

Date: 2021
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DOI: 10.1038/s41467-021-21407-w

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