Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma.

Détails

ID Serval
serval:BIB_DB65177C38F1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma.
Périodique
Nature
Auteur(s)
Tirosh I., Venteicher A.S., Hebert C., Escalante L.E., Patel A.P., Yizhak K., Fisher J.M., Rodman C., Mount C., Filbin M.G., Neftel C., Desai N., Nyman J., Izar B., Luo C.C., Francis J.M., Patel A.A., Onozato M.L., Riggi N., Livak K.J., Gennert D., Satija R., Nahed B.V., Curry W.T., Martuza R.L., Mylvaganam R., Iafrate A.J., Frosch M.P., Golub T.R., Rivera M.N., Getz G., Rozenblatt-Rosen O., Cahill D.P., Monje M., Bernstein B.E., Louis D.N., Regev A., Suvà M.L.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Statut éditorial
Publié
Date de publication
10/11/2016
Peer-reviewed
Oui
Volume
539
Numéro
7628
Pages
309-313
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management.
Mots-clé
Cell Differentiation, Cell Proliferation, DNA Copy Number Variations/genetics, Humans, Isocitrate Dehydrogenase/genetics, Neoplastic Stem Cells/metabolism, Neoplastic Stem Cells/pathology, Neural Stem Cells/metabolism, Neural Stem Cells/pathology, Neuroglia/metabolism, Neuroglia/pathology, Oligodendroglioma/genetics, Oligodendroglioma/pathology, Phylogeny, Point Mutation, Sequence Analysis, RNA, Single-Cell Analysis
Pubmed
Web of science
Création de la notice
27/07/2018 9:41
Dernière modification de la notice
20/08/2019 16:00
Données d'usage