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

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 be...

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Autores principales: Sancho-Martinez, Ignacio, Nivet, Emmanuel, Xia, Yun, Hishida, Tomoaki, Aguirre, Aitor, Ocampo, Alejandro, Ma, Li, Morey, Robert, Krause, Marie N., Zembrzycki, Andreas, Ansorge, Olaf, Vazquez-Ferrer, Eric, Dubova, Ilir, Reddy, Pradeep, Lam, David, Hishida, Yuriko, Wu, Min-Zu, Esteban, Concepcion Rodriguez, O'Leary, Dennis, Wahl, Geoffrey M., Verma, Inder M., Laurent, Louise C., Izpisua Belmonte, Juan Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764898/
https://www.ncbi.nlm.nih.gov/pubmed/26899176
http://dx.doi.org/10.1038/ncomms10743
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author Sancho-Martinez, Ignacio
Nivet, Emmanuel
Xia, Yun
Hishida, Tomoaki
Aguirre, Aitor
Ocampo, Alejandro
Ma, Li
Morey, Robert
Krause, Marie N.
Zembrzycki, Andreas
Ansorge, Olaf
Vazquez-Ferrer, Eric
Dubova, Ilir
Reddy, Pradeep
Lam, David
Hishida, Yuriko
Wu, Min-Zu
Esteban, Concepcion Rodriguez
O'Leary, Dennis
Wahl, Geoffrey M.
Verma, Inder M.
Laurent, Louise C.
Izpisua Belmonte, Juan Carlos
author_facet Sancho-Martinez, Ignacio
Nivet, Emmanuel
Xia, Yun
Hishida, Tomoaki
Aguirre, Aitor
Ocampo, Alejandro
Ma, Li
Morey, Robert
Krause, Marie N.
Zembrzycki, Andreas
Ansorge, Olaf
Vazquez-Ferrer, Eric
Dubova, Ilir
Reddy, Pradeep
Lam, David
Hishida, Yuriko
Wu, Min-Zu
Esteban, Concepcion Rodriguez
O'Leary, Dennis
Wahl, Geoffrey M.
Verma, Inder M.
Laurent, Louise C.
Izpisua Belmonte, Juan Carlos
author_sort Sancho-Martinez, Ignacio
collection PubMed
description 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.
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spelling pubmed-47648982016-03-04 Establishment of human iPSC-based models for the study and targeting of glioma initiating cells Sancho-Martinez, Ignacio Nivet, Emmanuel Xia, Yun Hishida, Tomoaki Aguirre, Aitor Ocampo, Alejandro Ma, Li Morey, Robert Krause, Marie N. Zembrzycki, Andreas Ansorge, Olaf Vazquez-Ferrer, Eric Dubova, Ilir Reddy, Pradeep Lam, David Hishida, Yuriko Wu, Min-Zu Esteban, Concepcion Rodriguez O'Leary, Dennis Wahl, Geoffrey M. Verma, Inder M. Laurent, Louise C. Izpisua Belmonte, Juan Carlos Nat Commun Article 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. Nature Publishing Group 2016-02-22 /pmc/articles/PMC4764898/ /pubmed/26899176 http://dx.doi.org/10.1038/ncomms10743 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sancho-Martinez, Ignacio
Nivet, Emmanuel
Xia, Yun
Hishida, Tomoaki
Aguirre, Aitor
Ocampo, Alejandro
Ma, Li
Morey, Robert
Krause, Marie N.
Zembrzycki, Andreas
Ansorge, Olaf
Vazquez-Ferrer, Eric
Dubova, Ilir
Reddy, Pradeep
Lam, David
Hishida, Yuriko
Wu, Min-Zu
Esteban, Concepcion Rodriguez
O'Leary, Dennis
Wahl, Geoffrey M.
Verma, Inder M.
Laurent, Louise C.
Izpisua Belmonte, Juan Carlos
Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
title Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
title_full Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
title_fullStr Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
title_full_unstemmed Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
title_short Establishment of human iPSC-based models for the study and targeting of glioma initiating cells
title_sort establishment of human ipsc-based models for the study and targeting of glioma initiating cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4764898/
https://www.ncbi.nlm.nih.gov/pubmed/26899176
http://dx.doi.org/10.1038/ncomms10743
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