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

Science
Publication type
Journal Article
Authors
Keywords
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
Journal
Science
Volume
360
Issue
6386
Pages
331-335
Date Published
2018 04 20
ISSN
1095-9203
DOI
10.1126/science.aao4750
PubMed ID
29674595
PubMed Central ID
PMC5949869
Links
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