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Nat Commun. 2016 Feb 22;7:10743. doi: 10.1038/ncomms10743.

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

Author information

1
Gene Expression Laboratory Belmonte, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
2
Universidad Católica San Antonio de Murcia (UCAM) Campus de los Jerónimos, N° 135 Guadalupe, Murcia 30107, Spain.
3
Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA.
4
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
5
Department of Neuropathology, West Wing, Level 1, John Radcliffe Hospital, Oxford OX3 9DU, UK.
6
Gene Expression Laboratory Wahl, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
7
Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

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 ∼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.

PMID:
26899176
PMCID:
PMC4764898
DOI:
10.1038/ncomms10743
[Indexed for MEDLINE]
Free PMC Article

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