Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis

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Expression of Idh1(R132H) 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, Sébastien; Lockstone, Helen; Freeman-Mills, Luke; Pfeffer, Inga; Sibson, Nicola; Goldin, Robert; Schuster-Böeckler, 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; Tomlinson, Ian.

In: Cancer Cell, Vol. 30, No. 4, 10.10.2016, p. 578-594.

Research output: Contribution to journalArticle

Harvard

Bardella, C, Al-Dalahmah, O, Krell, D, Brazauskas, P, Al-Qahtani, K, Tomkova, M, Adam, J, Serres, S, Lockstone, H, Freeman-Mills, L, Pfeffer, I, Sibson, N, Goldin, R, Schuster-Böeckler, B, Pollard, PJ, Soga, T, McCullagh, JS, Schofield, CJ, Mulholland, P, Ansorge, O, Kriaucionis, S, Ratcliffe, PJ, Szele, FG, Tomlinson, I & Tomlinson, I 2016, 'Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis', Cancer Cell, vol. 30, no. 4, pp. 578-594. https://doi.org/10.1016/j.ccell.2016.08.017

APA

Bardella, C., Al-Dalahmah, O., Krell, D., Brazauskas, P., Al-Qahtani, K., Tomkova, M., Adam, J., Serres, S., Lockstone, H., Freeman-Mills, L., Pfeffer, I., Sibson, N., Goldin, R., Schuster-Böeckler, B., Pollard, P. J., Soga, T., McCullagh, J. S., Schofield, C. J., Mulholland, P., ... Tomlinson, I. (2016). Expression of Idh1(R132H) 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

Vancouver

Author

Bardella, Chiara ; Al-Dalahmah, Osama ; Krell, Daniel ; Brazauskas, Pijus ; Al-Qahtani, Khalid ; Tomkova, Marketa ; Adam, Julie ; Serres, Sébastien ; Lockstone, Helen ; Freeman-Mills, Luke ; Pfeffer, Inga ; Sibson, Nicola ; Goldin, Robert ; Schuster-Böeckler, 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 ; Tomlinson, Ian. / Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis. In: Cancer Cell. 2016 ; Vol. 30, No. 4. pp. 578-594.

Bibtex

@article{67eb75b28ad54f6d8492e7e2549484c1,
title = "Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis",
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 Idh1(R132H) 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 α-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. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.",
keywords = "Animals, Brain Neoplasms, DNA Methylation, Glioma, Isocitrate Dehydrogenase, Lateral Ventricles, Mice, Mice, Transgenic, Mutation, Neoplastic Stem Cells, Stem Cell Niche, Transcriptome, Journal Article",
author = "Chiara Bardella and Osama Al-Dalahmah and Daniel Krell and Pijus Brazauskas and Khalid Al-Qahtani and Marketa Tomkova and Julie Adam and S{\'e}bastien Serres and Helen Lockstone and Luke Freeman-Mills and Inga Pfeffer and Nicola Sibson and Robert Goldin and Benjamin Schuster-B{\"o}eckler and Pollard, {Patrick J} and Tomoyoshi Soga and McCullagh, {James S} and Schofield, {Christopher J} and Paul Mulholland and Olaf Ansorge and Skirmantas Kriaucionis and Ratcliffe, {Peter J} and Szele, {Francis G} and Ian Tomlinson and Ian Tomlinson",
note = "Copyright {\textcopyright} 2016 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = oct,
day = "10",
doi = "10.1016/j.ccell.2016.08.017",
language = "English",
volume = "30",
pages = "578--594",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis

AU - Bardella, Chiara

AU - Al-Dalahmah, Osama

AU - Krell, Daniel

AU - Brazauskas, Pijus

AU - Al-Qahtani, Khalid

AU - Tomkova, Marketa

AU - Adam, Julie

AU - Serres, Sébastien

AU - Lockstone, Helen

AU - Freeman-Mills, Luke

AU - Pfeffer, Inga

AU - Sibson, Nicola

AU - Goldin, Robert

AU - Schuster-Böeckler, Benjamin

AU - Pollard, Patrick J

AU - Soga, Tomoyoshi

AU - McCullagh, James S

AU - Schofield, Christopher J

AU - Mulholland, Paul

AU - Ansorge, Olaf

AU - Kriaucionis, Skirmantas

AU - Ratcliffe, Peter J

AU - Szele, Francis G

AU - Tomlinson, Ian

AU - Tomlinson, Ian

N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2016/10/10

Y1 - 2016/10/10

N2 - Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) 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 α-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. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.

AB - Isocitrate dehydrogenase 1 mutations drive human gliomagenesis, probably through neomorphic enzyme activity that produces D-2-hydroxyglutarate. To model this disease, we conditionally expressed Idh1(R132H) 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 α-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. Idh1(R132H) mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.

KW - Animals

KW - Brain Neoplasms

KW - DNA Methylation

KW - Glioma

KW - Isocitrate Dehydrogenase

KW - Lateral Ventricles

KW - Mice

KW - Mice, Transgenic

KW - Mutation

KW - Neoplastic Stem Cells

KW - Stem Cell Niche

KW - Transcriptome

KW - Journal Article

U2 - 10.1016/j.ccell.2016.08.017

DO - 10.1016/j.ccell.2016.08.017

M3 - Article

C2 - 27693047

VL - 30

SP - 578

EP - 594

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 4

ER -