Building upon prior studies using hiPSC-derived 2D and 3D organoid cultures to study high-grade gliomas [1, 35, 39, 53] and medulloblastoma [63], we developed a humanized xenograft platform to model sporadic and NF1-associated pediatric LGGs and elucidate the pathogenesis, cellular origins, and signaling pathway dependencies. The gene discussed is NF1; the disease is central nervous system cancer.