Hovestadt, VolkerGoumnerova, LilianaSharma, TanviRusert, Jessica M.Wechsler-Reya, Robert J.Li, Xiao-NanPeyrl, AndreasGojo, JohannesKirchhofer, DominikLötsch, DanielaCzech, ThomasDorfer, ChristianHaberler, ChristineGeyeregger, ReneHalfmann, AngelaGawad, CharlesEaston, JohnPfister, Stefan M.Gajjar, AmarOrr, Brent A.Slavc, IreneRobinson, Giles W.Northcott, Paul A.Smith, KyleBihannic, LaureFilbin, MariellaShaw, McKenzieBaumgartner, AliciaDeWitt, JohnGroves, AndrewMayr, LisaWeisman, HannahRichman, AlyssaShore, MarniCarter, RobertPhoenix, TimothyHadley, JenniferTong, YiaiRivera, MiguelSuva, MarioHouston, JimAshmun, RichardDeCuypere, MichaelFlasch, DianeSilkov, AntoninaBernstein, BradleyLigon, KeithRozenblatt-Rosen, OritRegev, AvivPomeroy, ScottRosencrance, Celeste2022-07-272019-07-24Hovestadt, Volker, Kyle S. Smith, Laure Bihannic, Mariella G. Filbin, McKenzie L. Shaw, Alicia Baumgartner, John C. DeWitt, Andrew Groves, Lisa Mayr, Hannah R. Weisman, Alyssa R. Richman, Marni E. Shore, Liliana Goumnerova, Celeste Rosencrance, Robert A. Carter, Timothy N. Phoenix, Jennifer L. Hadley, Yiai Tong, Jim Houston, Richard A. Ashmun, Michael DeCuypere, Tanvi Sharma, Diane Flasch, Antonina Silkov, Keith L. Ligon, Scott L Pomeroy, Miguel N. Rivera, Orit Rozenblatt-Rosen, Jessica M. Rusert, Robert J. Wechsler-Reya, Xiao-Nan Li, Andreas Peyrl, Johannes Gojo, Dominik Kirchhofer, Daniela Lötsch, Thomas Czech, Christian Dorfer, Christine Haberler, Rene Geyeregger, Angela Halfmann, Charles Gawad, John Easton, Stefan M. Pfister, Aviv Regev, Amar Gajjar, Brent A Orr, Irene Slavc, Giles W. Robinson, Bradley E. Bernstein, Mario L. Suvà, and Paul A. Northcott. 2019. Resolving Medulloblastoma Cellular Architecture by Single-cell Genomics. Nature 572, no. 7767: 74-79.0028-08361476-4687https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37372884Medulloblastoma is a malignant childhood cerebellar tumour comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoural heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.en-USMultidisciplinaryJournal Article2022-07-2710.1038/s41586-019-1434-6