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

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.

Source: ScienceNOW - April 19, 2018 Category: Science Authors: Filbin, M. G., Tirosh, I., Hovestadt, V., Shaw, M. L., Escalante, L. E., Mathewson, N. D., Neftel, C., Frank, N., Pelton, K., Hebert, C. M., Haberler, C., Yizhak, K., Gojo, J., Egervari, K., Mount, C., van Galen, P., Bonal, D. M., Nguyen, Q.-D., Beck, A., Tags: Genetics, Medicine, Diseases reports Source Type: news