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1. Single-cell RNA-seq reveals that glioblastoma recapitulates normal brain development

Author

Kevin Petrecca, Jiannis Ragoussis, Mathieu Bourgey, Shamini Ayyadhury, Jack P. Antel, Redouane Allache, Charles P. Couturier, Phuong Uyen Le, Salma Baig, Changseok Lee, Yong Vw, Marie-Christine Guiot, Bratislav Misic, Jean Monlong, Xiaohua Yan, Gabriele Riva, Wang Ycd, and Guillaume Bourque

Subjects
education.field_of_study, Cell, Population, Cancer, Computational biology, Human brain, Biology, medicine.disease, Transcriptome, medicine.anatomical_structure, Cancer stem cell, Cancer cell, medicine, education, Progenitor
Abstract

SummaryCancer stem cells are critical for cancer initiation, development, and resistance to treatments. 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 38 296 glioblastoma cells and 22 637 normal human fetal brain cells. Using an unbiased approach, we mapped the lineage hierarchy of the developing human brain and compared the transcriptome of each cancer cell to this roadmap. We discovered a conserved neural trilineage cancer hierarchy with glial progenitor-like cells at the apex. We also found that this progenitor population contains the majority of cancer’s cycling cells and is the origin of heterogeneity. 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, unravels the origin of glioblastoma heterogeneity, and helps to identify cancer stem cell-specific targets.

Published
2018
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3. Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy.

Author

Couturier CP, Ayyadhury S, Le PU, Nadaf J, Monlong J, Riva G, Allache R, Baig S, Yan X, Bourgey M, Lee C, Wang YCD, Wee Yong V, Guiot MC, Najafabadi H, Misic B, Antel J, Bourque G, Ragoussis J, and Petrecca K

Subjects
Adult, Animals, Antineoplastic Agents, Alkylating pharmacology, Brain embryology, Brain Neoplasms pathology, Brain Neoplasms therapy, Cell Survival drug effects, Cell Survival genetics, Cells, Cultured, Female, Fetus, Glioblastoma pathology, Glioblastoma therapy, Humans, Mice, Inbred NOD, Mice, SCID, Neoplastic Stem Cells drug effects, Single-Cell Analysis methods, Temozolomide pharmacology, Xenograft Model Antitumor Assays methods, Brain metabolism, Brain Neoplasms genetics, Glioblastoma genetics, Neoplastic Stem Cells metabolism, Sequence Analysis, RNA methods, Transcriptome genetics
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.

Published
2020
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