Innate Neural Stem Cell Heterogeneity Determines the Patterning of Glioma Formation in Children

SummaryThe concept that gliomas comprise a heterogeneous group of diseases distinguished by their developmental origin raises the intriguing possibility that neural stem cells (NSCs) from different germinal zones have differential capacities to respond to glioma-causing genetic changes. We demonstrate that lateral ventricle subventricular zone NSCs are molecularly and functionally distinct from those of the third ventricle. Consistent with a unique origin for pediatric low-grade glioma, third ventricle, but not lateral ventricle, NSCs hyperproliferate in response to mutations characteristic of childhood glioma. Finally, we demonstrate that pediatric optic gliomas in Nf1 genetically engineered mice arise from the third ventricle. Collectively, these observations establish the importance of innate brain region NSC heterogeneity in the patterning of gliomagenesis in children and adults.

► lv-SVZ and TVZ neural stem cells (NSCs) are molecularly distinct populations
► TVZ and lv-SVZ NSCs differentially respond to glioma-associated mutations
► Third ventricle NSCs are the likely cell of origin for NF1 optic gliomas
► Innate brain region NSC heterogeneity partly dictates the pattern of gliomagenesis