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

Détails

ID Serval
serval:BIB_DEBCE3F8994E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.
Périodique
Science
Auteur⸱e⸱s
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., Sinai C., Czech T., Dorfer C., Goumnerova L., Lavarino C., Carcaboso A.M., Mora J., Mylvaganam R., Luo C.C., Peyrl A., Popović M., Azizi A., Batchelor T.T., Frosch M.P., Martinez-Lage M., Kieran M.W., Bandopadhayay P., Beroukhim R., Fritsch G., Getz G., Rozenblatt-Rosen O., Wucherpfennig K.W., Louis D.N., Monje M., Slavc I., Ligon K.L., Golub T.R., Regev A., Bernstein B.E., Suvà M.L.
ISSN
1095-9203 (Electronic)
ISSN-L
0036-8075
Statut éditorial
Publié
Date de publication
20/04/2018
Peer-reviewed
Oui
Volume
360
Numéro
6386
Pages
331-335
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Création de la notice
26/04/2018 18:02
Dernière modification de la notice
20/08/2019 16:03
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