RT Journal Article
SR Electronic
T1 Single-cell RNA-seq reveals that glioblastoma recapitulates normal brain development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 449439
DO 10.1101/449439
A1 Charles P. Couturier
A1 Shamini Ayyadhury
A1 Phuong U. Le
A1 Jean Monlong
A1 Gabriele Riva
A1 Redouane Allache
A1 Salma Baig
A1 Xiaohua Yan
A1 Mathieu Bourgey
A1 Changseok Lee
A1 Yu Chang David Wang
A1 V. Wee Yong
A1 Marie-Christine Guiot
A1 Bratislav Misic
A1 Jack Antel
A1 Guillaume Bourque
A1 Jiannis Ragoussis
A1 Kevin Petrecca
YR 2018
UL http://biorxiv.org/content/early/2018/10/22/449439.abstract
AB Summary Cancer 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.