Abstract
Glioblastoma (GBM) is the most common malignant brain tumor, and particularly difficult to treat due to its inherent heterogeneity, which is promoted by a variety of genetic drivers. A lack of models that robustly recapitulate heterogeneity has been a major obstacle for research progress on this disease. Here we show that neural progenitor cells derived from human induced pluripotent stem cells, CRISPR/Cas9 engineered with different combinations of authentic GBM-related genetic drivers give rise to GBM models that recapitulate the pathobiology of this tumor, including inter- and intra-tumor heterogeneity, differential drug sensitivity, extrachromosomal DNA amplifications, and rapid clonal evolution. Different models established with this approach could serve as a platform for longitudinal assessment of drug treatment sensitivity governed by subtype-specific driver mutations.
One Sentence Summary hiPSC-derived GBMs recapitulate disease.
