期刊
NATURE
卷 572, 期 7767, 页码 74-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-1434-6
关键词
-
资金
- Sontag Foundation Distinguished Scientist Award
- National Cancer Institute [R01CA232143-01, DP1CA216873]
- American Association for Cancer Research (NextGen Grant for Transformative Cancer Research)
- Brain Tumour Charity (Quest for Cures)
- American Lebanese Syrian Associated Charities (ALSAC)
- Howard Goodman Fellowship at MGH
- Merkin Institute Fellowship at the Broad Institute of MIT and Harvard
- Wang Family Fund
- V Foundation for Cancer Research
- Swiss National Science Foundation Sinergia program
- Alex's Lemonade Stand Foundation
- NIH Common Fund
- Human Frontier Science Program long-term fellowship [LT000596/2016-L]
- The Brain Tumour Charity [GN-000518]
- Burroughs Wellcome Fund
- K12 Paul Calabresi Career Award for Clinical Oncology [K12CA090354]
- Harvard Brain Cancer SPORE-Career Enhancement Program Award
- National Institutes of Health [3P30 CA006516-53S6]
- Cure Starts Now Foundation
- Solving Kids' Cancer/The Bibi Fund
- Andruzzi Foundation
- Austrian National Bank (OeNB Jubilaumsfonds Project) [15173]
- ALSF
- PBTF
- AKBTC
- CBJOLF
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据