This Thursday, May 6th, at 3 pm, Natalia Ochocka from the Laboratory of Molecular Neurobiology led by Prof. Bozena Kaminska, will give a lecture entitled "Single-cell RNA and protein sequencing reveals functional heterogeneity of glioma-associated brain macrophages"
Microglia and bone marrow-derived macrophages accumulate and adapt a tumor-supporting role in human malignant gliomas that show prevalence in men. Brain resident microglia and peripheral macrophages have different origins and transcriptomic profiles that suggest distinct functions in tumorigenesis. However, the heterogeneity of the cell functional phenotype and specific roles in gliomas remain elusive. Here, we show scRNA-seq combined with surface protein labeling of CD11b+ cells sorted from experimental GL261 gliomas. The identified marker proteins showed distinct spatial distribution of identified subsets in glioma-bearing brains. We demonstrate that although microglia and monocytes/macrophages activate similar transcriptional networks within the tumor environment, the responses of monocytes/macrophages are stronger, and they are localized predominantly within the tumor core. Monocytes/macrophages show substantial transcriptional heterogeneity allowing to distinguish subsequent differentiation states. The differentiated macrophages upregulated immune-suppressive genes and exhibited a high level of PD-L1 protein, which points to their role in suppression of the immune response against the tumor. Additionally, we studied whether there are sex differences in the transcriptomes of myeloid cells infiltrating gliomas and found higher expression of MHCII encoding genes in glioma-activated male microglia. This finding was corroborated in bulk and scRNA-seq data from human diffuse gliomas. Our results suggest that sex-specific gene expression in glioma-activated microglia may be relevant to differences in incidence and outcomes of glioma patients.
Meeting ID: 966 1729 0469