Human stem cell models for group 3 medulloblastoma uncover JARID1B as a regulator of the chromatin landscape.

ABSTRACT: Medulloblastoma (MB) is one of the most prevalent malignant brain tumors in children, with tremendous cognitive and neuroendocrine disability among survivors. Group 3 MB (G3MB) has poor overall survival at <50%, high frequencies of metastases, and no targeted therapies. Amplification of MYC and activation of TGFβ signaling occur frequently in G3MB. Many tumors have no reported mutations, suggesting epigenetic drivers. We here describe novel humanized models for G3MB from human induced pluripotent stem cells (hiPSC). By transducing hiPSC-derived neuroepithelial stem cells (NESC), we determined that: 1) both MYC and TGFβ effectors drove tumors in vivo; 2) MYC/TGFβR1 in combination led to more aggressive tumors and resistance to clinical inhibitors of TGFβ, and 3) NESC-derived t

SUBMITTER: Qadeer ZA 

PROVIDER: S-EPMC12709477 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature