Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
Details
Serval ID
serval:BIB_DEBCE3F8994E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
Journal
Science
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Publication state
Published
Issued date
20/04/2018
Peer-reviewed
Oui
Volume
360
Number
6386
Pages
331-335
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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 <i>PDGFRA</i> 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
Brain Neoplasms/genetics, Brain Neoplasms/pathology, Carcinogenesis/genetics, Cell Proliferation, Glioma/genetics, Glioma/pathology, Histones/metabolism, Humans, Mitogen-Activated Protein Kinase 7/genetics, Mutation, Oligodendroglia/metabolism, Oligodendroglia/pathology, Oncogenes, Receptor, Platelet-Derived Growth Factor alpha/genetics, Receptor, Platelet-Derived Growth Factor alpha/metabolism, Sequence Analysis, RNA/methods, Single-Cell Analysis/methods
Pubmed
Web of science
Create date
26/04/2018 19:02
Last modification date
20/08/2019 17:03