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

机译:先天性神经干细胞异质性决定儿童脑胶质瘤形成的模式。

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The 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.
机译:胶质瘤包括以其起源为特征的异质性疾病组的概念引起了一种有趣的可能性,即来自不同生发区的神经干细胞(NSC)对神经胶质瘤引起的遗传变化具有不同的反应能力。我们证明侧脑室脑室下区神经干细胞在分子和功能上不同于第三脑室。与儿童低度神经胶质瘤的独特起源,第三脑室而不是侧脑室一致,NSCs会因儿童神经胶质瘤的特征性突变而过度增殖。最后,我们证明Nf1基因工程小鼠中的小儿视神经胶质瘤来自第三脑室。总的来说,这些发现确立了先天性脑区NSC异质性在儿童和成人神经胶质瘤形成模式中的重要性。

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