Unravelling glioblastoma heterogeneity by means of single-cell RNA sequencing

• Published in: Cancer letters 2022-02, Vol.527, p.66-79
• Main Authors: Hernández Martínez, Ana, Madurga, Rodrigo, García-Romero, Noemí, Ayuso-Sacido, Ángel
• Format: Article
• Language: English
• Subjects: Biopsy; Brain cancer; Cancer; Data analysis; DNA polymerase; Gene expression; Genetic Heterogeneity; Genomes; Genomics; Glioblastoma; Glioblastoma - genetics; Humans; Intra-tumoral heterogeneity; Invasiveness; Mosaicism; Patients; Phenotypes; Ribonucleic acid; RNA; RNA-Seq - methods; scRNA-seq; Single-cell analysis; Single-Cell Analysis - methods; Stem cells; Therapeutic targets; Tumor microenvironment; Tumor microenvironment (TME); Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.12.008

Glioblastoma (GBM) is the most invasive and deadliest brain cancer in adults. Its inherent heterogeneity has been designated as the main cause of treatment failure. Thus, a deeper understanding of the diversity that shapes GBM pathobiology is of utmost importance. Single-cell RNA sequencing (scRNA-seq) technologies have begun to uncover the hidden composition of complex tumor ecosystems. Herein, a semi-systematic search of reference literature databases provided all existing publications using scRNA-seq for the investigation of human GBM. We compared and discussed findings from these works to build a more robust and unified knowledge base. All aspects ranging from inter-patient heterogeneity to intra-tumoral organization, cancer stem cell diversity, clonal mosaicism, and the tumor microenvironment (TME) are comprehensively covered in this report. Tumor composition not only differs across patients but also involves a great extent of heterogeneity within itself. Spatial and cellular heterogeneity can reveal tumor evolution dynamics. In addition, the discovery of distinct cell phenotypes might lead to the development of targeted treatment approaches. In conclusion, scRNA-seq expands our knowledge of GBM heterogeneity and helps to unravel putative therapeutic targets. •GBM heterogeneity hampers treatment efficacy and requires high-resolution characterization by means of scRNA-seq.•All TCGA subtypes are represented in individual GBM tumors.•GBM cancer cells adopt 4 states in which every putatively transformed cell expresses dissimilar GSC markers.•TME subpopulations have been identified and proposed as promising therapeutic targets for GBM immunotherapy.