TY - JOUR T1 - Single-cell RNA-seq reveals that glioblastoma recapitulates normal brain development JF - bioRxiv DO - 10.1101/449439 SP - 449439 AU - Charles P. Couturier AU - Shamini Ayyadhury AU - Phuong U. Le AU - Jean Monlong AU - Gabriele Riva AU - Redouane Allache AU - Salma Baig AU - Xiaohua Yan AU - Mathieu Bourgey AU - Changseok Lee AU - Yu Chang David Wang AU - V. Wee Yong AU - Marie-Christine Guiot AU - Bratislav Misic AU - Jack Antel AU - Guillaume Bourque AU - Jiannis Ragoussis AU - Kevin Petrecca Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/10/22/449439.abstract N2 - 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. ER -