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Nature DOI:10.1038/s41586-019-1434-6

Resolving medulloblastoma cellular architecture by single-cell genomics.

Publication TypeJournal Article
Year of Publication2019
AuthorsHovestadt, V, Smith, KS, Bihannic, L, Filbin, MG, Shaw, MKL, Baumgartner, A, DeWitt, JC, Groves, A, Mayr, L, Weisman, HR, Richman, AR, Shore, ME, Goumnerova, L, Rosencrance, C, Carter, RA, Phoenix, TN, Hadley, JL, Tong, Y, Houston, J, Ashmun, RA, DeCuypere, M, Sharma, T, Flasch, D, Silkov, A, Ligon, KL, Pomeroy, SL, Rivera, MN, Rozenblatt-Rosen, O, Rusert, JM, Wechsler-Reya, RJ, Li, X-N, Peyrl, A, Gojo, J, Kirchhofer, D, Lötsch, D, Czech, T, Dorfer, C, Haberler, C, Geyeregger, R, Halfmann, A, Gawad, C, Easton, J, Pfister, SM, Regev, A, Gajjar, A, Orr, BA, Slavc, I, Robinson, GW, Bernstein, BE, Suvà, ML, Northcott, PA
JournalNature
Volume572
Issue7767
Pages74-79
Date Published2019 08
ISSN1476-4687
KeywordsAdolescent, Adult, Animals, Cell Lineage, Cerebellum, Child, Child, Preschool, DNA Copy Number Variations, Gene Expression Regulation, Neoplastic, Genomics, Glutamic Acid, Humans, Infant, Medulloblastoma, Mice, Neurons, Single-Cell Analysis, Transcriptome
Abstract

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.

DOI10.1038/s41586-019-1434-6
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31341285?dopt=Abstract

Alternate JournalNature
PubMed ID31341285
PubMed Central IDPMC6754173
Grant ListDP2 CA239145 / CA / NCI NIH HHS / United States
DP1 CA216873 / CA / NCI NIH HHS / United States
R01 CA232143 / CA / NCI NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
P30 CA006516 / CA / NCI NIH HHS / United States