Volker Hovestadt, Kyle S. Smith, Laure Bihannic, Mariella G. Filbin together led this study of medulloblastoma cellular heterogeneity. Congratulations to the team!
Medulloblastoma is a malignant childhood cerebellar tumor type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behavior remains largely unexplored. The team used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. They found that WNT, SHH and Group 3 tumors comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumors consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumors closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumors exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes.
Taken together, this paper provides insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology. You can read the paper in Nature.