Single-cell RNA-seq study determines the ontogeny of macrophages in glioma

In their study of the tumor microenvironment of adult brain tumors, researchers from UCSF utilize single cell RNA-sequencing to characterize ontogeny-based heterogeneity of tumor-associated macrophages (TAMs). They answer the central question: Do macrophages, the big eaters of the immune system, and microglia, the resident macrophage equivalent in the brain, have different impact on brain tumors in adults?

The researchers performed single-cell RNA sequencing on cells sorted for CD11b as well as unsorted tissue using Fluidigm’s C1 and the droplet-based 10X Genomics to characterize a total of 5,455 single TAMs from 7 patients at UCSF. Combining this data with lineage-tracing information from two glioma mouse models via princliple component analysis allowed the researchers to distinguish macrophages from microglia and to identify transcriptional programs specific to each class. By crosslinking bulk RNA-seq data from public repositories, they find that microglia highly express pro-inflammatory molecules and reside in the tumor margin. Macrophages on the other hand mainly reside in the tumor core and express factors that support tumor growth and suppress other immune cells, like T-killer cells. Estimating the amount of macrophage and microglia infiltration in different glioma types revealed that high degree of infiltration with macrophages, but not with microglia, is associated with poor overall survival. Consequently, these results suggest to specifically target macrophages but not microglia in adult brain tumors.