Modeling Aggressive Medulloblastoma Using Human-Induced Pluripotent Stem Cells

Abstract : The goals of this project are to model MYC-driven medulloblastoma by using human stem cells and to further study the transcriptional mechanisms underlying the tumor formation process of MYC-driven medulloblastoma. Our current results strongly support that neural progenitors induced from human induced pluripotent stem cells by Atoh1 induction can be efficiently transformed by MYC oncogene to form aggressive brain tumors that recapitulate human MYC-driven group 3 medulloblastoma. We further show that it is feasible to establish neurosphere cultures from these medulloblastoma tumors to enrich brain tumor stem cells. This neurosphere culture model are suitable for studying gene functions and also testing novel therapies. Overall, this new MYC-driven medulloblastoma model we established provides a reliable model for developing and testing potential therapies for this highly aggressive pediatric brain tumors. It is also feasible to use this medulloblastoma model derived from human stem cells to perform personalized drug discovery and investigate the role of individual's distinctive genetic background in carcinogen sensitivity and medulloblastoma susceptibility.