Malignant granule cells can differentiate in patient SHH-MB and in mouse models of this disease.20,35,47,49,50 Interestingly, the activation of NEUROD1 in SHH-MB patient samples showed no dependency on TP53 mutational status (Supplementary Figure S4D), suggesting that differentiation processes can still be initiated in the presence of somatic TP53 mutations.51NEUROD1 was upregulated in a subpopulation of ONS-76 cells in tumor spheroids in co-culture with organoids compared to tumor monocultures (Figure 1E). Here, NEUROD1 is linked to neoplasm.