TY - JOUR
T1 - Innate Neural Stem Cell Heterogeneity Determines the Patterning of Glioma Formation in Children
AU - Lee, Da Yong
AU - Gianino, Scott M.
AU - Gutmann, David H.
N1 - Funding Information:
We thank Crystal White-Worsena and Madelyn Reynolds for technical assistance and Suzanne Baker (St. Jude Children's Research Hospital, Memphis, TN) for the GFAP-Cre ER mice. This work was funded by grants from the NIH (NS065547-01 to D.H.G.), NCI (CA141549-01 to D.H.G.), and the NEI (EY02687).
PY - 2012/7/10
Y1 - 2012/7/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863730854&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2012.05.036
DO - 10.1016/j.ccr.2012.05.036
M3 - Article
C2 - 22789544
AN - SCOPUS:84863730854
SN - 1535-6108
VL - 22
SP - 131
EP - 138
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -