YAP1/TAZ drives ependymoma-like tumour formation in mice

Noreen Eder; Federico Roncaroli; Marie-Charlotte Dolmart; Stuart Horswell; Felipe Andreiuolo; Helen R Flynn; Andre T Lopes; Suzanne Claxton; John-Paul Kilday; Lucy Collinson; Jun-Hao Mao; Torsten Pietsch; Barry Thompson; Ambrosius P Snijders; Sila K Ultanir

doi:10.1038/s41467-020-16167-y

YAP1/TAZ drives ependymoma-like tumour formation in mice

Noreen Eder, Federico Roncaroli, Marie-Charlotte Dolmart, Stuart Horswell, Felipe Andreiuolo, Helen R Flynn, Andre T Lopes, Suzanne Claxton, John-Paul Kilday, Lucy Collinson, Jun-Hao Mao, Torsten Pietsch, Barry Thompson, Ambrosius P Snijders, Sila K Ultanir

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2380
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16167-y
Publication status	Published - 13 May 2020

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title = "YAP1/TAZ drives ependymoma-like tumour formation in mice",

abstract = "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.",

author = "Noreen Eder and Federico Roncaroli and Marie-Charlotte Dolmart and Stuart Horswell and Felipe Andreiuolo and Flynn, {Helen R} and Lopes, {Andre T} and Suzanne Claxton and John-Paul Kilday and Lucy Collinson and Jun-Hao Mao and Torsten Pietsch and Barry Thompson and Snijders, {Ambrosius P} and Ultanir, {Sila K}",

year = "2020",

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doi = "10.1038/s41467-020-16167-y",

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T1 - YAP1/TAZ drives ependymoma-like tumour formation in mice

AU - Eder, Noreen

AU - Roncaroli, Federico

AU - Dolmart, Marie-Charlotte

AU - Horswell, Stuart

AU - Andreiuolo, Felipe

AU - Flynn, Helen R

AU - Lopes, Andre T

AU - Claxton, Suzanne

AU - Kilday, John-Paul

AU - Collinson, Lucy

AU - Mao, Jun-Hao

AU - Pietsch, Torsten

AU - Thompson, Barry

AU - Snijders, Ambrosius P

AU - Ultanir, Sila K

PY - 2020/5/13

Y1 - 2020/5/13

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-16167-y

DO - 10.1038/s41467-020-16167-y

M3 - Article

C2 - 32404936

SN - 2041-1723

VL - 11

SP - 2380

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

YAP1/TAZ drives ependymoma-like tumour formation in mice

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