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...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications Vol. 11; no. 1; pp. 3406 - 19
Main Authors: 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 08.07.2020
Nature Publishing Group
Nature Portfolio
Subjects:
13/100
13/106
13/31
13/51
14/19
14/5
38/91
59/5
631/67/1922
631/67/2329
631/67/71
64/60
Adult
Animals
Antineoplastic Agents, Alkylating - pharmacology
Brain
Brain - embryology
Brain - metabolism
Brain cancer
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Cancer
Cell Survival - drug effects
Cell Survival - genetics
Cells, Cultured
Female
Fetus
Fetuses
Gene expression
Gene sequencing
Glial stem cells
Glioblastoma
Glioblastoma - genetics
Glioblastoma - pathology
Glioblastoma - therapy
Glioblastoma cells
Heterogeneity
Humanities and Social Sciences
Humans
Life Sciences
Mice, Inbred NOD
Mice, SCID
multidisciplinary
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neural stem cells
Neuronal-glial interactions
Progenitor cells
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Sequence Analysis, RNA - methods
Single-Cell Analysis - methods
Stem cells
Target recognition
Temozolomide - pharmacology
Therapeutic applications
Transcriptome - genetics
Treatment resistance
Xenograft Model Antitumor Assays - methods
ISSN:2041-1723, 2041-1723
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Glioblastoma is thought to arise from neural stem cells. Here, to investigate this, the authors use single-cell RNA-sequencing to compare glioblastoma to the fetal human brain, and find a similarity between glial progenitor cells and a subpopulation of glioblastoma cells.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-17186-5