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

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 a...

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Autores principales: Couturier, Charles P., Ayyadhury, Shamini, Le, Phuong U., Nadaf, Javad, Monlong, Jean, Riva, Gabriele, Allache, Redouane, Baig, Salma, Yan, Xiaohua, Bourgey, Mathieu, Lee, Changseok, Wang, Yu Chang David, Wee Yong, V., Guiot, Marie-Christine, Najafabadi, Hamed, Misic, Bratislav, Antel, Jack, Bourque, Guillaume, Ragoussis, Jiannis, Petrecca, Kevin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343844/
https://www.ncbi.nlm.nih.gov/pubmed/32641768
http://dx.doi.org/10.1038/s41467-020-17186-5
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author Couturier, Charles P.
Ayyadhury, Shamini
Le, Phuong U.
Nadaf, Javad
Monlong, Jean
Riva, Gabriele
Allache, Redouane
Baig, Salma
Yan, Xiaohua
Bourgey, Mathieu
Lee, Changseok
Wang, Yu Chang David
Wee Yong, V.
Guiot, Marie-Christine
Najafabadi, Hamed
Misic, Bratislav
Antel, Jack
Bourque, Guillaume
Ragoussis, Jiannis
Petrecca, Kevin
author_facet Couturier, Charles P.
Ayyadhury, Shamini
Le, Phuong U.
Nadaf, Javad
Monlong, Jean
Riva, Gabriele
Allache, Redouane
Baig, Salma
Yan, Xiaohua
Bourgey, Mathieu
Lee, Changseok
Wang, Yu Chang David
Wee Yong, V.
Guiot, Marie-Christine
Najafabadi, Hamed
Misic, Bratislav
Antel, Jack
Bourque, Guillaume
Ragoussis, Jiannis
Petrecca, Kevin
author_sort Couturier, Charles P.
collection PubMed
description 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.
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spelling pubmed-73438442020-07-13 Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy Couturier, Charles P. Ayyadhury, Shamini Le, Phuong U. Nadaf, Javad Monlong, Jean Riva, Gabriele Allache, Redouane Baig, Salma Yan, Xiaohua Bourgey, Mathieu Lee, Changseok Wang, Yu Chang David Wee Yong, V. Guiot, Marie-Christine Najafabadi, Hamed Misic, Bratislav Antel, Jack Bourque, Guillaume Ragoussis, Jiannis Petrecca, Kevin Nat Commun Article 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. Nature Publishing Group UK 2020-07-08 /pmc/articles/PMC7343844/ /pubmed/32641768 http://dx.doi.org/10.1038/s41467-020-17186-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Couturier, Charles P.
Ayyadhury, Shamini
Le, Phuong U.
Nadaf, Javad
Monlong, Jean
Riva, Gabriele
Allache, Redouane
Baig, Salma
Yan, Xiaohua
Bourgey, Mathieu
Lee, Changseok
Wang, Yu Chang David
Wee Yong, V.
Guiot, Marie-Christine
Najafabadi, Hamed
Misic, Bratislav
Antel, Jack
Bourque, Guillaume
Ragoussis, Jiannis
Petrecca, Kevin
Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
title Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
title_full Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
title_fullStr Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
title_full_unstemmed Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
title_short Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
title_sort single-cell rna-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343844/
https://www.ncbi.nlm.nih.gov/pubmed/32641768
http://dx.doi.org/10.1038/s41467-020-17186-5
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