Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signaling
- Katerina Lawlor1,
- Maria Angeles Marques-Torrejon2,
- Gopuraja Dharmalingham3,
- Yasmine El-Azhar1,
- Michael D. Schneider1,
- Steven M. Pollard2 and
- Tristan A. Rodríguez1
- 1National Heart and Lung Institute, Imperial College London, London W12 0NN, United Kingdom;
- 2Centre for Regenerative Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh EH16 4UU, United Kingdom;
- 3MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Imperial College London, London W12 0NN, United Kingdom
- Corresponding authors: tristan.rodriguez{at}imperial.ac.uk, steven.pollard{at}ed.ac.uk
Abstract
There is increasing evidence demonstrating that adult neural stem cells (NSCs) are a cell of origin of glioblastoma. Here we analyzed the interaction between transformed and wild-type NSCs isolated from the adult mouse subventricular zone niche. We found that transformed NSCs are refractory to quiescence-inducing signals. Unexpectedly, we also demonstrated that these cells induce quiescence in surrounding wild-type NSCs in a cell–cell contact and Notch signaling-dependent manner. Our findings therefore suggest that oncogenic mutations are propagated in the stem cell niche not just through cell-intrinsic advantages, but also by outcompeting neighboring stem cells through repression of their proliferation.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.336917.120.
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Freely available online through the Genes & Development Open Access option.
- Received January 16, 2020.
- Accepted October 1, 2020.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
