Dissecting human gliomas by single-cell RNA sequencing

Abstract

Diffuse gliomas are the most common human primary brain tumors and remain incurable. They are complex entities in which diverse genetic and nongenetic effects determine tumor biology and clinical course. Our current understanding of gliomas in patients is primarily based on genomic and transcriptomic methods that have profiled them as bulk, providing critical information yet masking the diversity of cells within each tumor. Recent advances in single-cell DNA and RNA profiling have paved the way to studying tumors at cellular resolution. Here, we review initial studies deploying single-cell analysis in clinical glioma samples, with a focus on RNA expression profiling. We highlight how these studies provide new insights into glioma biology, tumor heterogeneity, cancer cell lineages, cancer stem cell programs, the tumor microenvironment, and glioma classification.

Keywords: diffuse gliomas; heterogeneity; single-cell RNA sequencing.

Fig. 1

Single-cell RNA-seq in clinical gliomas. (A) Pipeline for single-cell expression profiling and analysis from tumor samples. (B) Single-cell RNA-seq can provide information on malignant cell lineages,^, cancer stem programs,^, cell cycle, malignant cell genetics (copy number variation, point mutations, genetic rearrangements),^,, the tumor microenvironment, and tumor classification (eg, TCGA subtypes). Abbreviations: Cla: classical; Mes: mesenchymal; Pro: proneural. Figure adapted from references.^,,