Single-cell multi-omics analysis identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma [ATAC_seq]

We perform scMultiomic sequencing on matched patient primary and recurrent tumors. We identify a unique population of cells that is metabolically and epigenetically altered. We recapitulate this population of cells in in vivo radiation resistant models. Disruption of this population with wtIDH1 inhibitors suppresses growth and re-sensitizes cells to irradiation. Overall design: senisitive and IR esistant D458 cells were treated with an IDH1i (IDH305 or GSK321) for 48hrs. 50,000 cells were then isolated for ATAC assay and library sequencing