Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis

Citations Over TimeTop 10% of 2016 papers

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 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. Idh1R132H mutation in the major adult neurogenic stem cell niche causes a phenotype resembling gliomagenesis.

Related Papers

• → Enriched Environment Increases Neural Stem/Progenitor Cell Proliferation and Neurogenesis in the Subventricular Zone of Stroke-Lesioned Adult Rats(2005)249 cited
• AGING OF THE SUBVENTRICULAR ZONE NEURAL STEM CELL NICHE.(2011)
• → A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells(2006)150 cited
• → To Become or Not to Become Tumorigenic: Subventricular Zone Versus Hippocampal Neural Stem Cells(2020)21 cited
• → Depletion of neural stem cells from the subventricular zone of adult mouse brain using cytosine b‐Arabinofuranoside(2015)7 cited