An integrated perspective on single-cell and spatial transcriptomic signatures in high-grade gliomas.

Abstract

High-grade gliomas (HGG) are incurable brain malignancies in children and adults. Breakthrough advances in transcriptomic technologies unveiled the intricate diversity of cellular states and their spatial organization within HGGs. We qualitatively integrated 55 neoplastic transcriptomic signatures described in 17 single-cell and spatial RNA sequencing-based studies. Our review delineates a spectrum of cellular states, represented by the expression of specific genes, which can be conceptualized along a "reactive-developmental programs" axis. Additionally, we discussed the potential cues influencing these cellular states, including how spatial organization may impact transcriptomic dynamics. Leveraging these insightful discoveries, we discussed a novel, evolutive way to integrate the different transcriptomic signatures in two or three dimensions, incorporating developmental states, their proliferative capacity, and their possible transition towards reactive states. This integrated analysis illuminates the diverse cellular landscape of HGGs and provides a valuable resource for further elucidation of malignant mechanisms, and for the design of therapeutic endeavors.