TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression

Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor-parenchymal cells may promote specific phases of disease-progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell-population, by conditional Sox2-knockout, drastically reduced glioblastoma-vascularization and -size. Hence, TAMEP emerge as a tumor-parenchymal component with strong impact on glioblastoma progression.