Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
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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 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. |
Year of Publication | 2018
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Journal | Science
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Volume | 360
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Issue | 6386
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Pages | 331-335
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Date Published | 2018 04 20
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ISSN | 1095-9203
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DOI | 10.1126/science.aao4750
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PubMed ID | 29674595
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PubMed Central ID | PMC5949869
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Grant list | R01 CA188228 / CA / NCI NIH HHS / United States
DP1 CA216873 / CA / NCI NIH HHS / United States
U24 CA180922 / CA / NCI NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P01 CA142536 / CA / NCI NIH HHS / United States
K12 CA090354 / CA / NCI NIH HHS / United States
S10 RR023440 / RR / NCRR NIH HHS / United States
R33 CA202820 / CA / NCI NIH HHS / United States
R01 CA215489 / CA / NCI NIH HHS / United States
R01 CA219943 / CA / NCI NIH HHS / United States
P50 CA165962 / CA / NCI NIH HHS / United States
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