Single-cell multi-omics analysis identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma [PDX 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 PDX411 xenograft MB tumors according to 10xGenomics protocol for cyropreserved tissue. Human cells were isolated using the miltenyi mouse cell depletion kit. Nuclei were then isolated using the 10x genomica protocol and submitted for scMultiomic sequencing.