Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Filbin, MG, Tirosh, I, Hovestadt, V, Shaw, MKL, Escalante, LE, Mathewson, ND, Neftel, C, Frank, N, Pelton, K, Hebert, CM, Haberler, C, Yizhak, K, Gojo, J, Egervari, K, Mount, C, van Galen, P, Bonal, DM, De Nguyen, Q-, Beck, A, Sinai, C, Czech, T, Dorfer, C, Goumnerova, L, Lavarino, C, Carcaboso, AM, Mora, J, Mylvaganam, R, Luo, CC, Peyrl, A, Popović, M, Azizi, A, Batchelor, TT, Frosch, MP, Martinez-Lage, M, Kieran, MW, Bandopadhayay, P, Beroukhim, R, Fritsch, G, Getz, G, Rozenblatt-Rosen, O, Wucherpfennig, KW, Louis, DN, Monje, M, Slavc, I, Ligon, KL, Golub, TR, Regev, A, Bernstein, BE, Suvà, ML |
Journal | Science |
Volume | 360 |
Issue | 6386 |
Pages | 331-335 |
Date Published | 2018 04 20 |
ISSN | 1095-9203 |
Keywords | Brain Neoplasms, Carcinogenesis, Cell Proliferation, Glioma, Histones, Humans, Mitogen-Activated Protein Kinase 7, Mutation, Oligodendroglia, Oncogenes, Receptor, Platelet-Derived Growth Factor alpha, Sequence Analysis, RNA, Single-Cell Analysis |
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. |
DOI | 10.1126/science.aao4750 |
Pubmed | |
Alternate Journal | Science |
PubMed ID | 29674595 |
PubMed Central ID | PMC5949869 |
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 |
Science DOI:10.1126/science.aao4750
Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
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