A Functional Role of OLIG2 in Tumor Heterogeneity of MYC-amplified Medulloblastoma

To study how radiation alters the different types of cells during tumor recurrence in high-risk MYC-amplified MB, we performed scRNA-seq using the 10X Genomics scRNA-seq platform to compare the primary untreated tumors, residual tumors immediately following radiotherapy, and the spontaneously recurrent tumors 7-8 weeks post-irradiation using OLIG2-high MB002 PDX. We found that:1, the variety of cell types demonstrated that the MYC-amplified MB PDX tumors were heterogenous communities, comprising diverse cell types in a broad range differentiation states and developmental trajectories, and included the host-derived cells of the tumor microenvironment; 2, Radiation-induced transient changes in cellular heterogeneity that resolved as tumor recurred; 3, Recurrent tumors showed global changes in gene expression compared to primary tumors Overall design: We dissected tumors from the brains of 3 replicate PDX mice from 3 conditions, primary untreated tumors, residual tumors immediately following radiotherapy, and the spontaneously recurrent tumors 7-8 weeks post-irradiation using OLIG2-high MB002 PDX. We dissociated the samples, and FAC-sorted the human cells using the mCherry marker. We then processed the sorted cells using the 10X Genomics scRNA-seq platform and sequenced the resulting libraries.