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The Heterogeneous Cellular States of Glioblastoma Stem Cells Revealed by Single Cell Analysis
27 Pages Posted: 19 Jan 2022
More...Abstract
Glioblastoma stem cells (GSCs) contributed to glioblastoma (GBM) treatment resistance and relapse. However, the current researches on GSCs are performed usually outside the human tumor microenvironment, and the cellular states of primary GSCs need to be elucidated. In this study, we leveraged single-cell transcriptome sequencing data of six independent GBM cohorts, and combined lineage and stemness features to identify primary GSCs. As a result, we constructed a cellular hierarchy where GSCs resident in the center. In addition, we identified and characterized two different and recurrent GSCs subpopulations: proliferative GSCs (pGSCs) and quiescent GSCs (qGSCs). The pGSCs showed high cell cycle activity, indicating rapid cell division, while qGSCs showed a quiescence state. Then we traced the processes of tumor development by pseudo-time analysis and tumor phylogeny. Interestingly, GSCs accumulated throughout the whole tumor development period, where pGSCs contributed to the early stage and qGSCs were enriched in the later stage. Finally, we constructed an 8-gene prognostic signature reflecting pGSCs activity and found that patients with a high pGSCs activity had poor clinical outcomes. Our study highlights the primary GSCs heterogeneity and its correlation to tumor development and clinical outcomes, which indicates potential treatment targets for GBM.
Funding Information: This work was supported by the National Natural Science Foundation of China [Grant Nos. 31801116, 82173321, 32000459 and 81802926], the China Postdoctoral Science Foundation (2018M641842), the Heilongjiang Postdoctoral Foundation (LBH-Z17160).
Declaration of Interests: The authors declare no conflict of interest.
Keywords: single-cell sequencing, glioblastoma, glioblastoma stem cells, heterogeneity
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