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Article Dans Une Revue Nature Communications Année : 2016

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

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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.
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hal-01477820 , version 1 (09-01-2020)

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