Chiara Bardella
Expression of Idh1R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis
Bardella, Chiara; Al-Dalahmah, Osama; Krell, Daniel; Brazauskas, Pijus; Al-Qahtani, Khalid; Tomkova, Marketa; Adam, Julie; Serres, Sebastien; Lockstone, Helen; Freeman-Mills, Luke; Pfeffer, Inga; Sibson, Nicola; Goldin, Robert; Schuster-B�eckler, Benjamin; Pollard, Patrick J.; Soga, Tomoyoshi; McCullagh, James S.; Schofield, Christopher J.; Mulholland, Paul; Ansorge, Olaf; Kriaucionis, Skirmantas; Ratcliffe, Peter J.; Szele, Francis G.; Tomlinson, Ian
Authors
Osama Al-Dalahmah
Daniel Krell
Pijus Brazauskas
Khalid Al-Qahtani
Marketa Tomkova
Julie Adam
SEBASTIEN SERRES Sebastien.Serres@nottingham.ac.uk
Assistant Professor in Metabolic Biochemistry
Helen Lockstone
Luke Freeman-Mills
Inga Pfeffer
Nicola Sibson
Robert Goldin
Benjamin Schuster-B�eckler
Patrick J. Pollard
Tomoyoshi Soga
James S. McCullagh
Christopher J. Schofield
Paul Mulholland
Olaf Ansorge
Skirmantas Kriaucionis
Peter J. Ratcliffe
Francis G. Szele
Ian Tomlinson
Abstract
Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. The mice developed hydrocephalus and grossly dilated lateral ventricles, with accumulation of 2-hydroxyglutarate and reduced ?-ketoglutarate. Stem and transit amplifying/progenitor cell populations were expanded, and proliferation increased. Cells expressing SVZ markers infiltrated surrounding brain regions. SVZ cells also gave rise to proliferative subventricular nodules. DNA methylation was globally increased, while hydroxymethylation was decreased. Mutant SVZ cells overexpressed Wnt, cell-cycle and stem cell genes, and shared an expression signature with human gliomas. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.
Citation
Bardella, C., Al-Dalahmah, O., Krell, D., Brazauskas, P., Al-Qahtani, K., Tomkova, M., …Tomlinson, I. (2016). Expression of Idh1R132H in the murine subventricular zone stem cell niche recapitulates features of early gliomagenesis. Cancer Cell, 30(4), 578-594. https://doi.org/10.1016/j.ccell.2016.08.017
Journal Article Type | Article |
---|---|
Acceptance Date | Aug 29, 2016 |
Online Publication Date | Sep 29, 2016 |
Publication Date | Oct 10, 2016 |
Deposit Date | Mar 8, 2017 |
Publicly Available Date | Mar 28, 2024 |
Journal | Cancer Cell |
Print ISSN | 1535-6108 |
Electronic ISSN | 1878-3686 |
Publisher | Elsevier (Cell Press) |
Peer Reviewed | Peer Reviewed |
Volume | 30 |
Issue | 4 |
Pages | 578-594 |
DOI | https://doi.org/10.1016/j.ccell.2016.08.017 |
Public URL | http://www.ncbi.nlm.nih.gov/pubmed/27693047 |
Publisher URL | https://www.sciencedirect.com/science/article/pii/S1535610816304020?via%3Dihub |
Additional Information | This article is maintained by: Elsevier; Article Title: Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis; Journal Title: Cancer Cell; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ccell.2016.08.017; Content Type: article; Copyright: © 2016 The Author(s). Published by Elsevier Inc. |
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