Unravelling glioblastoma heterogeneity by means of single-cell RNA sequencing.
Author: Hernández Martínez, Ana; Madurga Lacalle, Rodrigo; García Romero, Noemí; Ayuso Sacido, Ángel
Abstract: 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.
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