Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells
Evelyn Susanto, Ana Marín Navarro, Leilei Zhou, Anders Sundström, Niek van Bree, Marina Stantic, Mohsen Moslem, Jignesh Tailor, Jonne Rietdijk, Verónica Zubillaga, Jens-Martin Hübner, Holger Weishaupt, Johanna Wolfsberger, Irina Alafuzoff, Ann Nordgren, Thierry Magnaldo, Peter Siesjö, John Inge Johnsen, Marcel Kool, Kristiina Tammimies, Anna Darabi, Fredrik J. Swartling, Anna Falk, Margareta Wilhelm
Abstract
Significance Here we describe and utilize a model of medulloblastoma, a malignancy accounting for 20% of all childhood brain cancers. We used iPS-derived neural stem cells with a familial mutation causing aberrant SHH signaling. We show that these cells, when transplanted into mouse cerebellum, form tumors that mimics SHH-driven medulloblastoma, demonstrating the development of cancer from healthy neural stem cells in vivo. Our results show that reprogramming of somatic cells carrying familial cancer mutations can be used to model the initiation and progression of childhood cancer.