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

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. We isolated nuclei from matched primary and recurrent group 3 and group 4 MB tumors according to 10xGenomics protocol for cyropreserved tissue. Nuclei were submitted for scMultiomic sequencing.