Author/Editor		Filbin, Mariella G.; Tirosh, Itay; Horvestadt, Volker; McKenzie, Shaw L.; Escalante, Leah E.; Mathewson, Nathan D.; Neftel, Cyril; Frank, Nelli; Pelton, Kristine; Popović, Mara
Title		Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq
Type		članek
Vol. and No.		Letnik 360, št. 6386
Publication year		2018
Volume		str. 331-335
ISSN		1095-9203 - Science (New York, N.Y.)
Language		eng
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 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.
Keywords		gliomi centralni živčni sistem genski subkloni gliomas central nervous system genetic subclones