Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy

Charles P. Couturier, Shamini Ayyadhury, Phuong U. Le, Javad Nadaf, Jean Monlong, Gabriele Riva, Redouane Allache, Salma Baig, Xiaohua Yan, Mathieu Bourgey, Changseok Lee, Yu Chang David Wang, V. Wee Yong, Marie-Christine Guiot, Hamed Najafabadi, Bratislav Misic, Jack Antel, Guillaume Bourque, Jiannis Ragoussis and Kevin Petrecca ()
Additional contact information
Charles P. Couturier: McGill University
Shamini Ayyadhury: McGill University
Phuong U. Le: McGill University
Javad Nadaf: McGill University
Jean Monlong: McGill University
Gabriele Riva: McGill University
Redouane Allache: McGill University
Salma Baig: McGill University
Xiaohua Yan: McGill University
Mathieu Bourgey: McGill University
Changseok Lee: McGill University
Yu Chang David Wang: McGill University
V. Wee Yong: University of Calgary
Marie-Christine Guiot: McGill University
Hamed Najafabadi: McGill University
Bratislav Misic: McGill University
Jack Antel: McGill University
Guillaume Bourque: McGill University
Jiannis Ragoussis: McGill University
Kevin Petrecca: McGill University

Nature Communications, 2020, vol. 11, issue 1, 1-19

Abstract: Abstract Cancer stem cells are critical for cancer initiation, development, and treatment resistance. Our understanding of these processes, and how they relate to glioblastoma heterogeneity, is limited. To overcome these limitations, we performed single-cell RNA sequencing on 53586 adult glioblastoma cells and 22637 normal human fetal brain cells, and compared the lineage hierarchy of the developing human brain to the transcriptome of cancer cells. We find a conserved neural tri-lineage cancer hierarchy centered around glial progenitor-like cells. We also find that this progenitor population contains the majority of the cancer’s cycling cells, and, using RNA velocity, is often the originator of the other cell types. Finally, we show that this hierarchal map can be used to identify therapeutic targets specific to progenitor cancer stem cells. Our analyses show that normal brain development reconciles glioblastoma development, suggests a possible origin for glioblastoma hierarchy, and helps to identify cancer stem cell-specific targets.

Date: 2020
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DOI: 10.1038/s41467-020-17186-5

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