|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|
|Date Published||2018 Apr 20|
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.