Mapping the single cell transcriptome reveals the cellular composition of ATRT subgroups

Atypical Teratoid/Rhabdoid Tumors (ATRTs) are paediatric brain cancers, occurring mostly in infants. The driving mutation is a biallelic loss of the SMARCB1 gene, a member of the SWI/SNF complex. Epigenetic studies revealed three distinct molecular subgroups of ATRTs (TYR, SHH, MYC) associated with specific clinical and (epi)genomic features. To survey the cellular composition of the three ATRT subgroups, we performed single nucleus RNA-sequencing of 25.000 cells from 12 ATRT samples (TYR: 3, SHH: 6, MYC: 3). Overall tSNE clustering analyses of the RNA data revealed distinct tumor and non-tumor cell populations (such as microglia), the latter most abundantly present in MYC and SHH. Moreover, we detected one cluster of cells, almost exclusively present in TYR that exhibited the transcriptomic profile of neuronal stem cells. On the contrary, SHH harboured many tumor cells that displayed an OPC like differentiation. In summary, single cell transcriptome analyses revealed communalities and differences in the cellular composition of ATRTs, revealing different stem cell-like cell populations in each ATRT subgroup and suggesting that each subgroup may have a different cell of origin.