Resolving medulloblastoma cellular architecture by single-cell genomics.

Nature
Authors
Keywords
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.

Year of Publication
2019
Journal
Nature
Volume
572
Issue
7767
Pages
74-79
Date Published
2019 08
ISSN
1476-4687
DOI
10.1038/s41586-019-1434-6
PubMed ID
31341285
PubMed Central ID
PMC6754173
Links
Grant list
DP2 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