This article investigates the multilayered transcriptional architecture of glioblastoma (GBM) ecosystems, focusing on tumor heterogeneity, which is a key driver of therapeutic resistance in this aggressive brain cancer. The authors utilized single-nucleus RNA sequencing and bulk DNA sequencing on a large cohort of GBM samples to identify distinct malignant cellular states, including novel ones, and to characterize intertumor heterogeneity through baseline gene expression programs. The research further explores the complex interplay between the tumor microenvironment (TME) and malignant cells, highlighting how TME influences cellular states and overall tumor profiles. Finally, the study examines genetic associations with these identified transcriptional patterns, defining three stereotypic GBM ecosystems that integrate cellular composition, malignant states, and baseline profiles with specific genetic alterations.
References:
