biostudies-literatureBlanco-Carmona EEuropean Research CouncilDeutsche ForschungsgemeinschaftWellcome Trust3260-3275https://www.ebi.ac.uk/biostudies/studies/S-EPMC12916745biostudies-literatureUnknown27(12)<h4>Background</h4>Atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive pediatric central nervous system tumors defined by the inactivation of the SMARCB1 gene. Despite the identification of three distinct molecular subtypes, each defined by unique clinical and molecular characteristics, no subtype-specific therapeutic strategies are currently available. This highlights an urgent need to deepen our understanding of the cellular heterogeneity and developmental origins of ATRTs.<h4>Methods</h4>We generated a comprehensive single-nucleus transcriptomic atlas of ATRT samples, integrated it with single-nucleus ATAC-seq and spatial transcriptomics data, and validated our findings experimentally using patient-derived ATRT tumoroid models.<h4>Results</h4>Our analyses revealed distinct sNeuro-oncologyA cycling, progenitor-like cell population at the base of atypical teratoid rhabdoid tumor subtype differentiation trajectories.PMC12916745223135/Z/21/ZJO 1598/1-1850571Thomas CKool MDeMartino JPfister SMKorshunov AKranendonk MEGDrost JJohann PDPaassen IShaw MDonson AMBullesbach AFilbin MGMauermann MBrok MHe JJager NBuhl JLStraathof KHoving EWAnderson NBehjati SVibhakar RForeman NKHasselblatt MFederico ABlanco-Carmona EFruhwald MCFranke NfalseA cycling, progenitor-like cell population at the base of atypical teratoid rhabdoid tumor subtype differentiation trajectories.<h4>Background</h4>Atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive pediatric central nervous system tumors defined by the inactivation of the SMARCB1 gene. Despite the identification of three distinct molecular subtypes, each defined by unique clinical and molecular characteristics, no subtype-specific therapeutic strategies are currently available. This highlights an urgent need to deepen our understanding of the cellular heterogeneity and developmental origins of ATRTs.<h4>Methods</h4>We generated a comprehensive single-nucleus transcriptomic atlas of ATRT samples, integrated it with single-nucleus ATAC-seq and spatial transcriptomics data, and validated our findings experimentally using patient-derived ATRT tumoroid models.<h4>Results</h4>Our analyses revealed distinct s2025-01-01T00:00:00Z2025 Dec2026-07-09T11:26:04.038Z2026-07-09T10:47:08.042ZS-EPMC129167454072614710.1093/neuonc/noaf179