TY - JOUR TI - Single-cell chromatin accessibility profiling of glioblastoma identifies an invasive cancer stem cell population associated with lower survival AU - Guilhamon, Paul AU - Chesnelong, Charles AU - Kushida, Michelle M AU - Nikolic, Ana AU - Singhal, Divya AU - MacLeod, Graham AU - Madani Tonekaboni, Seyed Ali AU - Cavalli, Florence MG AU - Arlidge, Christopher AU - Rajakulendran, Nishani AU - Rastegar, Naghmeh AU - Hao, Xiaoguang AU - Hassam, Rozina AU - Smith, Laura J AU - Whetstone, Heather AU - Coutinho, Fiona J AU - Nadorp, Bettina AU - Ellestad, Katrina I AU - Luchman, H Artee AU - Chan, Jennifer Ai-wen AU - Shoichet, Molly S AU - Taylor, Michael D AU - Haibe-Kains, Benjamin AU - Weiss, Samuel AU - Angers, Stephane AU - Gallo, Marco AU - Dirks, Peter B AU - Lupien, Mathieu A2 - Postovit, Lynne-Marie A2 - Struhl, Kevin A2 - Verhaak, Roel VL - 10 PY - 2021 DA - 2021/01/11 SP - e64090 C1 - eLife 2021;10:e64090 DO - 10.7554/eLife.64090 UR - https://doi.org/10.7554/eLife.64090 AB - Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary human GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In-depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival, in line with the higher invasive properties of Invasive state GSCs compared to Reactive and Constructive GSCs as shown by in vitro and in vivo assays. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies. KW - Glioblastoma KW - cancer stem cell KW - tumor initiating cells KW - ATAC KW - single cell ATAC KW - chromatin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -