School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Mol Syst Biol. 2021 Jun;17(6):e9522. doi: 10.15252/msb.20209522.
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.
单细胞 RNA 测序已成为解析与正常和恶性发育过程相关的细胞状态的强大工具。在这里，我们使用 scRNA-seq 来研究扩增的人类神经干细胞 (hNSC) 的细胞周期状态。从这些数据中，我们构建了一个细胞周期分类器，可识别哺乳动物神经发生过程中和神经胶质瘤中神经上皮衍生细胞类型中的传统细胞周期相和假定的静止样状态。神经 G0 标志物富含静止 NSC 基因和其他在非分裂神经祖细胞中发现的神经发育标记物。推定的神经胶质瘤干细胞样细胞在神经 G0 细胞群中明显富集。神经 G0 细胞群和基因表达与侵袭性较低的肿瘤和神经胶质瘤患者的生存时间延长显著相关。鉴定神经 G0 调节剂的遗传筛选表明，与 Hippo/Yap 和 p53 通路相关的基因敲除减少了体外的神经 G0，导致 G1 期更快过渡，静止相关标志物下调，以及神经 G0 基因表达丧失。因此，神经 G0 代表了在神经上皮衍生细胞和神经胶质瘤中发现的动态静止样状态。
