Single-cell multi-omics analysis identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma [scRNA-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. D458 xenograft tumors were harvested from the cerebellum of mice. Tumors were chopped with razor blades and dissociated in RPMI media. Live cell suspensions were flow sorted based on green fluorescent protein (GFP) expression on a MoFlo XDP-Flex (Beckman Coulter) and 2,000/L GFP+ cells were submitted to the University of Colorado Genomics core for scRNA sequencing with the Chromium X. N=6