Lineage specification in glioblastoma is regulated by METTL7B

Myrianni Constantinou; James Nicholson; Xinyu Zhang; Eleni Maniati; Sara Lucchini; Gabriel Rosser; Claire Vinel; Jun Wang; Yau Mun Lim; Sebastian Brandner; Sven Nelander; Sara Badodi; Silvia Marino

Cell Reports (Jun 2024)

Lineage specification in glioblastoma is regulated by METTL7B

Myrianni Constantinou,
James Nicholson,
Xinyu Zhang,
Eleni Maniati,
Sara Lucchini,
Gabriel Rosser,
Claire Vinel,
Jun Wang,
Yau Mun Lim,
Sebastian Brandner,
Sven Nelander,
Sara Badodi,
Silvia Marino

Affiliations

Myrianni Constantinou: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
James Nicholson: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Xinyu Zhang: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Eleni Maniati: Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6AS, UK
Sara Lucchini: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Gabriel Rosser: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Claire Vinel: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Jun Wang: Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6AS, UK
Yau Mun Lim: Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, and Department of Neurodegenerative Disease, Queen Square, Institute of Neurology, University College London, Queen Square, London, UK
Sebastian Brandner: Division of Neuropathology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, and Department of Neurodegenerative Disease, Queen Square, Institute of Neurology, University College London, Queen Square, London, UK
Sven Nelander: Department of Immunology Genetics and Pathology, Uppsala University, Uppsala, Sweden
Sara Badodi: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK
Silvia Marino: Brain Tumour Research Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK; Corresponding author

Journal volume & issue: Vol. 43, no. 6
p. 114309

Abstract

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Summary: Glioblastomas are the most common malignant brain tumors in adults; they are highly aggressive and heterogeneous and show a high degree of plasticity. Here, we show that methyltransferase-like 7B (METTL7B) is an essential regulator of lineage specification in glioblastoma, with an impact on both tumor size and invasiveness. Single-cell transcriptomic analysis of these tumors and of cerebral organoids derived from expanded potential stem cells overexpressing METTL7B reveal a regulatory role for the gene in the neural stem cell-to-astrocyte differentiation trajectory. Mechanistically, METTL7B downregulates the expression of key neuronal differentiation players, including SALL2, via post-translational modifications of histone marks.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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