Establishment of human iPSC-based models for the study and targeting of glioma initiating cells.

Détails

ID Serval
serval:BIB_22042A157C2B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells.
Périodique
Nature communications
Auteur⸱e⸱s
Sancho-Martinez I., Nivet E., Xia Y., Hishida T., Aguirre A., Ocampo A., Ma L., Morey R., Krause M.N., Zembrzycki A., Ansorge O., Vazquez-Ferrer E., Dubova I., Reddy P., Lam D., Hishida Y., Wu M.Z., Esteban C.R., O'Leary D., Wahl G.M., Verma I.M., Laurent L.C., Izpisua Belmonte J.C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
22/02/2016
Peer-reviewed
Oui
Volume
7
Pages
10743
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Glioma tumour-initiating cells (GTICs) can originate upon the transformation of neural progenitor cells (NPCs). Studies on GTICs have focused on primary tumours from which GTICs could be isolated and the use of human embryonic material. Recently, the somatic genomic landscape of human gliomas has been reported. RTK (receptor tyrosine kinase) and p53 signalling were found dysregulated in ∼90% and 86% of all primary tumours analysed, respectively. Here we report on the use of human-induced pluripotent stem cells (hiPSCs) for modelling gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo transplantation of transformed iNPCs leads to highly aggressive tumours containing undifferentiated stem cells and their differentiated derivatives. Metabolic modulation compromises GTIC viability. Last, screening of 101 anti-cancer compounds identifies three molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results highlight the potential of hiPSCs for studying human tumourigenesis.
Mots-clé
Cell Line, Tumor, Cell Transformation, Neoplastic, Female, Glioma/etiology, Humans, Induced Pluripotent Stem Cells, Male, Neoplastic Stem Cells/physiology, Neural Stem Cells/physiology, SOXB1 Transcription Factors/metabolism, Tumor Stem Cell Assay
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/08/2018 9:32
Dernière modification de la notice
20/08/2019 12:58
Données d'usage