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

Author

Listed:
  • Claire Vinel

    (Queen Mary University London)

  • Gabriel Rosser

    (Queen Mary University London)

  • Loredana Guglielmi

    (Queen Mary University London)

  • Myrianni Constantinou

    (Queen Mary University London)

  • Nicola Pomella

    (Queen Mary University London)

  • Xinyu Zhang

    (Queen Mary University London)

  • James R. Boot

    (Queen Mary University London)

  • Tania A. Jones

    (Queen Mary University London)

  • Thomas O. Millner

    (Queen Mary University London)

  • Anaelle A. Dumas

    (Queen Mary University London)

  • Vardhman Rakyan

    (Queen Mary University London)

  • Jeremy Rees

    (University College London Hospitals NHS Foundation Trust)

  • Jamie L. Thompson

    (University of Nottingham)

  • Juho Vuononvirta

    (Queen Mary University London)

  • Suchita Nadkarni

    (Queen Mary University London)

  • Tedani El Assan

    (University College London Hospitals NHS Foundation Trust)

  • Natasha Aley

    (UCL Queen Square Institute of Neurology)

  • Yung-Yao Lin

    (Queen Mary University London
    Queen Mary University of London)

  • Pentao Liu

    (The University of Hong Kong)

  • Sven Nelander

    (Uppsala University)

  • Denise Sheer

    (Queen Mary University London)

  • Catherine L. R. Merry

    (University of Nottingham)

  • Federica Marelli-Berg

    (Queen Mary University London)

  • Sebastian Brandner

    (University College London Hospitals NHS Foundation Trust
    UCL Queen Square Institute of Neurology)

  • Silvia Marino

    (Queen Mary University London)

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.

Suggested Citation

  • Claire Vinel & Gabriel Rosser & Loredana Guglielmi & Myrianni Constantinou & Nicola Pomella & Xinyu Zhang & James R. Boot & Tania A. Jones & Thomas O. Millner & Anaelle A. Dumas & Vardhman Rakyan & Je, 2021. "Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26297-6
    DOI: 10.1038/s41467-021-26297-6
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