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...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Nature communications Jg. 11; H. 1; S. 3406 - 19
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 08.07.2020 Nature Publishing Group Nature Portfolio
Schlagworte:	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-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
Bibliographie:	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