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Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq

Author(s)
Regev, Aviv
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Abstract
Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.
Date issued
2018-04
URI
https://hdl.handle.net/1721.1/125052
Department
David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Filbin, Mariella G. et al. “Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.” Science 360 (2018): 331-335 © 2018 The Author(s)
Version: Author's final manuscript
ISSN
0193-4511

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