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|a Regev, Aviv
|e author
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|a Massachusetts Institute of Technology. Department of Biology
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|a Koch Institute for Integrative Cancer Research at MIT
|e contributor
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|a Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq
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|b American Association for the Advancement of Science (AAAS),
|c 2020-05-06T15:28:49Z.
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|z Get fulltext
|u https://hdl.handle.net/1721.1/125052
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|a 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.
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|a National Cancer Institute (U.S.) (Grant 1U24CA180922)
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|a National Cancer Institute (U.S.) (Grant R33CA202820)
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|a National Cancer Institute (U.S.) (Grant P30-CA14051)
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|a en
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|a Article
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|t 10.1126/SCIENCE.AAO4750
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|t Science
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