Tmic-29. distinct molecular signatures of microglia and bone-marrow macrophages in the glioma perivascular niche

Tumor associated macrophage (TAM) infiltration correlates with glioma grade and invasiveness. TAMs are comprised of brain-resident microglia and bone-marrow monocyte derived cells, which extravasate the blood-brain barrier. Study of the distinct roles of these two populations of TAMs has been confounded by their overlapping and inducible gene expression profiles. To identify durable and specific gene-expression signatures for TAMs of microglial and bone-marrow origin respectively, we profiled regional biopsies of primary, untreated gliomas using single-cell and bulk sequencing. In 4 glioblastomas and 2 low-grade gliomas, we single-cell mRNA sequenced 672 TAMs from regional biopsies of the infiltrated white matter, the enhancing edge, and the tumor core. Exome-sequencing was also performed on bulk DNA-extractions from each biopsy, and matched blood. Additionally, we single-cell sequenced microglia derived from non-malignant human neocortex and we reanalyzed single-cell and bulk mRNA sequencing data of microglia and bone-marrow macrophages in human and mouse. Based on this, we identified a signature of specific purinergic receptors and other genes that is: 1) differentially expressed between non-malignant microglia and bone-marrow macrophages, across multiple samples and ages; 2) correlated with CX3CR1 and CD11b expression in TAMs extracted from patient biopsies at the mRNA and protein level; 3) enriched in the infiltrated white matter; 4) is conserved in mo...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research