TY  - JOUR
AU  - Hovestadt, Volker
AU  - Smith, Kyle S
AU  - Bihannic, Laure
AU  - Filbin, Mariella G
AU  - Shaw, McKenzie L
AU  - Baumgartner, Alicia
AU  - DeWitt, John C
AU  - Groves, Andrew
AU  - Mayr, Lisa
AU  - Weisman, Hannah R
AU  - Richman, Alyssa R
AU  - Shore, Marni E
AU  - Goumnerova, Liliana
AU  - Rosencrance, Celeste
AU  - Carter, Robert A
AU  - Phoenix, Timothy N
AU  - Hadley, Jennifer L
AU  - Tong, Yiai
AU  - Houston, Jim
AU  - Ashmun, Richard A
AU  - DeCuypere, Michael
AU  - Sharma, Tanvi
AU  - Flasch, Diane
AU  - Silkov, Antonina
AU  - Ligon, Keith L
AU  - Pomeroy, Scott L
AU  - Rivera, Miguel N
AU  - Rozenblatt-Rosen, Orit
AU  - Rusert, Jessica M
AU  - Wechsler-Reya, Robert J
AU  - Li, Xiao-Nan
AU  - Peyrl, Andreas
AU  - Gojo, Johannes
AU  - Kirchhofer, Dominik
AU  - Lötsch, Daniela
AU  - Czech, Thomas
AU  - Dorfer, Christian
AU  - Haberler, Christine
AU  - Geyeregger, Rene
AU  - Halfmann, Angela
AU  - Gawad, Charles
AU  - Easton, John
AU  - Pfister, Stefan M
AU  - Regev, Aviv
AU  - Gajjar, Amar
AU  - Orr, Brent A
AU  - Slavc, Irene
AU  - Robinson, Giles W
AU  - Bernstein, Bradley E
AU  - Suvà, Mario L
AU  - Northcott, Paul A
TI  - Resolving medulloblastoma cellular architecture by single-cell genomics.
JO  - Nature 
VL  - 572
IS  - 7767
SN  - 1476-4687
CY  - London [u.a.]
PB  - Nature Publ. Group52462
M1  - DKFZ-2019-01902
SP  - 74 - 79
PY  - 2019
AB  - Medulloblastoma is a malignant childhood cerebellar tumour 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 behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 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 consisted exclusively 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, 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. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.
LB  - PUB:(DE-HGF)16
C6  - pmid:31341285
DO  - DOI:10.1038/s41586-019-1434-6
UR  - https://inrepo02.dkfz.de/record/144450
ER  -