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

Ignacio Sancho-Martinez*, Emmanuel Nivet, Yun Xia, Tomoaki Hishida, Aitor Aguirre, Alejandro Ocampo, Li Ma, Robert Morey, Marie N. Krause, Andreas Zembrzycki, Olaf Ansorge, Eric Vazquez-Ferrer, Ilir Dubova, Pradeep Reddy, David Lam, Yuriko Hishida, Min Zu Wu, Concepcion Rodriguez Esteban, Dennis Oleary, Geoffrey M. WahlInder M. Verma, Louise C. Laurent, Juan Carlos Izpisua Belmonte

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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 â1/490% 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.

Original languageEnglish (US)
Article number10743
JournalNature Communications
Volume7
DOIs
StatePublished - Feb 22 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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