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

Abstract : Glioma tumour-initiating cells (GTICs) can originate upon the ă transformation of neural progenitor cells (NPCs). Studies on GTICs have ă focused on primary tumours from which GTICs could be isolated and the ă use of human embryonic material. Recently, the somatic genomic landscape ă of human gliomas has been reported. RTK (receptor tyrosine kinase) and ă p53 signalling were found dysregulated in similar to 90% and 86% of ă all primary tumours analysed, respectively. Here we report on the use of ă human-induced pluripotent stem cells (hiPSCs) for modelling ă gliomagenesis. Dysregulation of RTK and p53 signalling in hiPSC-derived ă NPCs (iNPCs) recapitulates GTIC properties in vitro. In vivo ă transplantation of transformed iNPCs leads to highly aggressive tumours ă containing undifferentiated stem cells and their differentiated ă derivatives. Metabolic modulation compromises GTIC viability. Last, ă screening of 101 anti-cancer compounds identifies three molecules ă specifically targeting transformed iNPCs and primary GTICs. Together, ă our results highlight the potential of hiPSCs for studying human ă tumourigenesis.
Type de document :
Article dans une revue
Nature Communications, Nature Publishing Group, 2016, 7, 〈10.1038/ncomms10743〉
Liste complète des métadonnées

https://hal.archives-ouvertes.fr/hal-01477820
Contributeur : Michel Khrestchatisky <>
Soumis le : lundi 27 février 2017 - 16:49:27
Dernière modification le : mardi 10 avril 2018 - 09:24:28

Lien texte intégral

Identifiants

Collections

Citation

Ignacio Sancho-Martinez, Emmanuel Nivet, Yun Xia, Ă Tomoaki Hishida, Aitor Aguirre, et al.. Establishment of human iPSC-based models for the study and targeting of ă glioma initiating cells. Nature Communications, Nature Publishing Group, 2016, 7, 〈10.1038/ncomms10743〉. 〈hal-01477820〉

Partager

Métriques

Consultations de la notice

98