Neural G0: a quiescent‐like state found in neuroepithelial‐derived cells and glioma
Samantha O’Connor, Heather Feldman, Sonali Arora, Pia Hoellerbauer, Chad M. Toledo, Philip Corrin, Lucas Carter, Megan Kufeld, Hamid Bolouri, Ryan Basom, Jeffrey J. Delrow, José L. McFaline‐Figueroa, Cole Trapnell, Steven M. Pollard, Anoop P. Patel, Patrick J. Paddison, Christopher Plaisier
Abstract
Single-cell RNA sequencing has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA-seq to examine the cell cycle states of expanding human neural stem cells (hNSCs). From these data, we constructed a cell cycle classifier that identifies traditional cell cycle phases and a putative quiescent-like state in neuroepithelial-derived cell types during mammalian neurogenesis and in gliomas. The Neural G0 markers are enriched with quiescent NSC genes and other neurodevelopmental markers found in non-dividing neural progenitors. Putative glioblastoma stem-like cells were significantly enriched in the Neural G0 cell population. Neural G0 cell populations and gene expression are significantly associated with less aggressive tumors and extended patient survival for gliomas. Genetic screens to identify modulators of Neural G0 revealed that knockout of genes associated with the Hippo/Yap and p53 pathways diminished Neural G0 in vitro, resulting in faster G1 transit, down-regulation of quiescence-associated markers, and loss of Neural G0 gene expression. Thus, Neural G0 represents a dynamic quiescent-like state found in neuroepithelial-derived cells and gliomas.