biostudies-literatureLi CNCI NIH HHSNational Cancer Institute of the National Institutes of Healthe186344https://www.ebi.ac.uk/biostudies/studies/S-EPMC11949068biostudies-literatureUnknown10(5)Glioblastoma (GBM) is the most lethal brain cancer, with GBM stem cells (GSCs) driving therapeutic resistance and recurrence. Targeting GSCs offers a promising strategy for preventing tumor relapse and improving outcomes. We identify SUV39H1, a histone-3, lysine-9 methyltransferase, as critical for GSC maintenance and GBM progression. SUV39H1 is upregulated in GBM compared with normal brain tissues, with single-cell RNA-seq showing its expression predominantly in GSCs due to super-enhancer-mediated activation. Knockdown of SUV39H1 in GSCs impaired their proliferation and stemness. Whole-cell RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. By integrating the RNA-seq data with ATAC-seq data, we further demoJCI insightSUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma.PMC11949068P30CA030199R01 CA231349P30 CA082709P30 CA030199Shen JLi CWang YASpruck CHuang TYDu YXie QNephew KPCao BGhosh SVo GVCarpenter RLLu QRfalseSUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma.Glioblastoma (GBM) is the most lethal brain cancer, with GBM stem cells (GSCs) driving therapeutic resistance and recurrence. Targeting GSCs offers a promising strategy for preventing tumor relapse and improving outcomes. We identify SUV39H1, a histone-3, lysine-9 methyltransferase, as critical for GSC maintenance and GBM progression. SUV39H1 is upregulated in GBM compared with normal brain tissues, with single-cell RNA-seq showing its expression predominantly in GSCs due to super-enhancer-mediated activation. Knockdown of SUV39H1 in GSCs impaired their proliferation and stemness. Whole-cell RNA-seq analysis revealed that SUV39H1 regulates G2/M cell cycle progression, stem cell maintenance, and cell death pathways in GSCs. By integrating the RNA-seq data with ATAC-seq data, we further demo2025-01-01T00:00:00Z2025 Mar2026-06-02T06:33:12.862Z2025-07-11T03:03:56.419ZS-EPMC119490684005982910.1172/jci.insight.186344