Single-Cell Transcriptome Analysis of Lineage Diversity and Microenvironment in High-Grade Glioma

Despite extensive molecular characterization, we lack a comprehensive picture of lineage identity, differentiation, and microenvironmental composition in high-grade gliomas (HGGs). We sampled the cellular milieu of HGGs with massively-parallel single-cell RNA-Seq. While HGG cells can resemble glia or even immature neurons and form branched lineage structures, mesenchymal transformation results in unstructured populations. Glioma cells in a subset of mesenchymal tumors lose their neural lineage identity, express inflammatory genes, and co-exist with marked myeloid infiltration, implying a molecular interaction between glioma and immune cells. Finally, we found that myeloid cells can resemble microglia, macrophages, or a hybrid state, and enrichment of these cells is predictive of poor survival. Overall design: Performed single cell RNA-seq on tens of thousands of dissociated high-grade glioma tissue cells from 8 human patients.