Single-cell chromatin accessibility profiling of glioblastoma identifies an invasive cancer stem cell population associated with lower survival.

Autor:	Guilhamon P; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Chesnelong C; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Kushida MM; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Nikolic A; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada., Singhal D; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada., MacLeod G; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada., Madani Tonekaboni SA; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Canada., Cavalli FM; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Arlidge C; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Rajakulendran N; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada., Rastegar N; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Hao X; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.; Department of Cell Biology & Anatomy, University of Calgary, Calgary, Canada., Hassam R; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.; Department of Cell Biology & Anatomy, University of Calgary, Calgary, Canada., Smith LJ; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada., Whetstone H; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Coutinho FJ; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada., Nadorp B; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada., Ellestad KI; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada., Luchman HA; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.; Department of Cell Biology & Anatomy, University of Calgary, Calgary, Canada., Chan JA; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Canada., Shoichet MS; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada., Taylor MD; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada.; Division of Neurosurgery, University of Toronto, Toronto, Canada.; Departments of Molecular Genetics and Surgery, University of Toronto, Toronto, Canada., Haibe-Kains B; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Canada.; Department of Computer Science, University of Toronto, Toronto, Canada.; Ontario Institute for Cancer Research, Toronto, Canada.; Vector Institute, Toronto, Canada., Weiss S; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.; Department of Cell Biology & Anatomy, University of Calgary, Calgary, Canada.; Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada., Angers S; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Canada., Gallo M; Clark Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Canada.; Department of Physiology & Pharmacology, University of Calgary, Calgary, Canada., Dirks PB; Developmental and Stem Cell Biology Program and Arthur and Sonia Labatt Brain tumor Research Centre, The Hospital for Sick Children, Toronto, Canada.; Division of Neurosurgery, University of Toronto, Toronto, Canada.; Ontario Institute for Cancer Research, Toronto, Canada., Lupien M; Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jan 11; Vol. 10. Date of Electronic Publication: 2021 Jan 11.
DOI:	10.7554/eLife.64090
Abstrakt:	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. Competing Interests: PG, CC, MK, AN, DS, GM, SM, FC, CA, NR, NR, XH, RH, LS, HW, FC, BN, KE, HL, JC, MS, MT, BH, SW, SA, MG, PD, ML No competing interests declared (© 2021, Guilhamon et al.)
Databáze:	MEDLINE
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