Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma.

Vinel, Claire; Rosser, Gabriel; Guglielmi, Loredana; Constantinou, Myrianni; Pomella, Nicola; Zhang, Xinyu; Boot, James R; Jones, Tania A; Millner, Thomas O; Dumas, Anaelle A; Rakyan, Vardhman; Rees, Jeremy; Thompson, Jamie L; Vuononvirta, Juho; Nadkarni, Suchita; El Assan, Tedani; Aley, Natasha; Lin, Yung-Yao; Liu, Pentao; Nelander, Sven; Sheer, Denise; Merry, Catherine L R; Marelli-Berg, Federica; Brandner, Sebastian; Marino, Silvia

Vinel, Claire; Rosser, Gabriel; Guglielmi, Loredana; Constantinou, Myrianni; Pomella, Nicola; Zhang, Xinyu; Boot, James R; Jones, Tania A; Millner, Thomas O; Dumas, Anaelle A; Rakyan, Vardhman; Rees, Jeremy; Thompson, Jamie L; Vuononvirta, Juho; Nadkarni, Suchita; El Assan, Tedani; Aley, Natasha; Lin, Yung-Yao; Liu, Pentao; Nelander, Sven; Sheer, Denise; Merry, Catherine L R; Marelli-Berg, Federica; Brandner, Sebastian; Marino, Silvia.

Affiliation

Vinel C; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Rosser G; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Guglielmi L; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Constantinou M; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Pomella N; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Zhang X; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Boot JR; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Jones TA; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Millner TO; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Dumas AA; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Rakyan V; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Rees J; Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK.
Thompson JL; Stem Cell Glycobiology Group, Biodiscovery Institute, University of Nottingham, Nottingham, UK.
Vuononvirta J; The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Nadkarni S; The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
El Assan T; Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK.
Aley N; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
Lin YY; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Liu P; Stem Cell Laboratory, National Bowel Research Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 2 Newark Street, London, UK.
Nelander S; Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Hong Kong, Hong Kong.
Sheer D; Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Merry CLR; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Marelli-Berg F; Stem Cell Glycobiology Group, Biodiscovery Institute, University of Nottingham, Nottingham, UK.
Brandner S; The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK.
Marino S; Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK.

Nat Commun ; 12(1): 6130, 2021 10 21.

Article in En | MEDLINE | ID: mdl-34675201

ABSTRACT

ABSTRACT

Epigenetic mechanisms which play an essential role in normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC) are also responsible for some of the changes in the glioblastoma (GBM) genome. Here we develop a strategy to compare the epigenetic and transcriptional make-up of primary GBM cells (GIC) with patient-matched expanded potential stem cell (EPSC)-derived NSC (iNSC). Using a comparative analysis of the transcriptome of syngeneic GIC/iNSC pairs, we identify a glycosaminoglycan (GAG)-mediated mechanism of recruitment of regulatory T cells (Tregs) in GBM. Integrated analysis of the transcriptome and DNA methylome of GBM cells identifies druggable target genes and patient-specific prediction of drug response in primary GIC cultures, which is validated in 3D and in vivo models. Taken together, we provide a proof of principle that this experimental pipeline has the potential to identify patient-specific disease mechanisms and druggable targets in GBM.

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neoplastic Stem Cells / Brain Neoplasms / Glioblastoma / Neural Stem Cells Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2021 Document type: Article Affiliation country: Reino Unido

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