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Shared molecular regulation of quiescence in neural and glioma stem cells reveals therapeutic vulnerabilities

ABSTRACT: Quiescent glioma cells evade chemoradiation and drive glioblastoma recurrence by reactivating to repopulate the tumour, but are hard to study due to their rarity and difficulty maintaining quiescence in vitro. We hypothesised that quiescence programs conserved between neural stem cells and glioma cells could be exploited to lock glioma cells in quiescence and prevent reactivation. Using single-cell RNA-sequencing and patient-derived glioma stem cell lines, we found that although glioma cells resist entering deep quiescence, they share conserved activation trajectories with neural stem cells. Because this conservation lets a tractable neural progenitor line act as a surrogate for rare quiescent glioma cells, we queried LINCS L1000 signatures across more than 3,000 compounds and validated the top classes (mTOR, ATPase and histone lysine methyltransferase inhibitors) as quiescence promoters in glioma stem cell lines. By establishing conserved activation programs and enabling cross-cell-type screening, our work provides a strategy for driving therapy-resistant glioma cells into quiescence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE349283 | GEO | 2026/10/01

REPOSITORIES: GEO

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