| Autor: |
Eder, Noreen, Roncaroli, Federico, Dolmart, Marie-Charlotte, Horswell, Stuart, Andreiuolo, Felipe, Flynn, Helen R., Lopes, Andre T., Claxton, Suzanne, Kilday, John-Paul, Collinson, Lucy, Mao, Jun-Hao, Pietsch, Torsten, Thompson, Barry, Snijders, Ambrosius P., Ultanir, Sila K. |
| Předmět: |
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| Zdroj: |
Nature Communications; 5/13/2020, Vol. 11 Issue 1, p1-16, 16p |
| Abstrakt: |
YAP1 gene fusions have been observed in a subset of paediatric ependymomas. Here we show that, ectopic expression of active nuclear YAP1 (nlsYAP5SA) in ventricular zone neural progenitor cells using conditionally-induced NEX/NeuroD6-Cre is sufficient to drive brain tumour formation in mice. Neuronal differentiation is inhibited in the hippocampus. Deletion of YAP1's negative regulators LATS1 and LATS2 kinases in NEX-Cre lineage in double conditional knockout mice also generates similar tumours, which are rescued by deletion of YAP1 and its paralog TAZ. YAP1/TAZ-induced mouse tumours display molecular and ultrastructural characteristics of human ependymoma. RNA sequencing and quantitative proteomics of mouse tumours demonstrate similarities to YAP1-fusion induced supratentorial ependymoma. Finally, we find that transcriptional cofactor HOPX is upregulated in mouse models and in human YAP1-fusion induced ependymoma, supporting their similarity. Our results show that uncontrolled YAP1/TAZ activity in neuronal precursor cells leads to ependymoma-like tumours in mice. YAP1 gene fusions are found in subgroups of paediatric ependymomas. Here the authors show that YAP1 activation in NeuroD6 positive neuronal precursor cells can induce ependymoma-like tumours in mice. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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