Neural G0: a quiescent‐like state found in neuroepithelial‐derived cells and glioma. Issue 6 (8th June 2021)

• Record Type: Journal Article
• Authors: O'Connor, Samantha A; Feldman, Heather M; Arora, Sonali; Hoellerbauer, Pia; Toledo, Chad M; Corrin, Philip; Carter, Lucas; Kufeld, Megan; Bolouri, Hamid; Basom, Ryan; Delrow, Jeffrey; McFaline‐Figueroa, José L; Trapnell, Cole; Pollard, Steven M; Patel, Anoop; Paddison, Patrick J; Plaisier, Christopher L
• Is Part Of: Molecular systems biology. Volume 17:Issue 6(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-08
• Subjects: G0 -- glioma -- neural stem cells -- quiescence -- scRNA‐seq; Molecular biology -- Periodicals; Systems biology -- Periodicals; 572.8
• DOI: 10.15252/msb.20209522
• Languages: English
• ISSNs: 1744-4292

Abstract

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. SYNOPSIS: scRNA‐seq and functional genomics are applied to human neural stem cells to characterize cell cycle phases and factors increasing proliferative rate. A new cell cycle state "Neural G0" is discovered, offering insights into glioma patient tumors and patient survival. Unsupervised cell clustering reveals eight distinct cell cycle phases in human neural stem cells. A novel Neural G0 cell cycle phase is characterized by up‐regulation of genes with key roles in neural development. Increased expression of a GBM‐specific Neural G0 gene signature is associated with better prognosis for glioma patients, independent of tumor grade and IDH1/2 mutation. A functional‐genomics screen identifies genes that alter the time spent in G0/G1‐like states thereby increasing the proliferative rate of neural stem cells. Abstract : scRNA‐seq and functional genomics are applied to human neural stem cells to characterize cell cycle phases and factors increasing proliferative rate. A new cell cycle state "Neural G0" is discovered, offering insights into glioma patient tumors and patient survival.