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Notch1 switches progenitor competence in inducing medulloblastoma

The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in...

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Main Authors: Ballabio, Claudio (Author) , Gianesello, Matteo (Author) , Lago, Chiara (Author) , Okonechnikov, Konstantin (Author) , Anderle, Marica (Author) , Aiello, Giuseppe (Author) , Antonica, Francesco (Author) , Zhang, Tingting (Author) , Gianno, Francesca (Author) , Giangaspero, Felice (Author) , Hassan, Bassem A. (Author) , Pfister, Stefan (Author) , Tiberi, Luca (Author)
Format: Article (Journal)
Language:English
Published: 23 Jun 2021
In: Science advances
Year: 2021, Volume: 7, Issue: 26, Pages: 1-13
ISSN:2375-2548
DOI:10.1126/sciadv.abd2781
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/sciadv.abd2781
Verlag, lizenzpflichtig, Volltext: https://www.webofscience.com/api/gateway?GWVersion=2&SrcAuth=DynamicDOIArticle&SrcApp=WOS&KeyAID=10.1126%2Fsciadv.abd2781&DestApp=DOI&SrcAppSID=EUW1ED0A6DWkauDRZWxohELriO3fR&SrcJTitle=SCIENCE+ADVANCES&DestDOIRegistrantName=American+Association+for+the+Advancement+of+Science+%28AAAS%29
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Author Notes:Claudio Ballabio, Matteo Gianesello, Chiara Lago, Konstantin Okonechnikov, Marica Anderle, Giuseppe Aiello, Francesco Antonica, Tingting Zhang, Francesca Gianno, Felice Giangaspero, Bassem A. Hassan, Stefan M. Pfister, Luca Tiberi
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Summary:The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b(+) cells are competent to initiate group 3 MB, and we observed that S100b(+) cells have higher levels of Notch1 pathway activity compared to Math1(+) cells. We found that additional activation of Notch1 in Math1(+) and Sox2(+) cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.
Item Description:Gesehen am 19.07.2022
Physical Description:Online Resource
ISSN:2375-2548
DOI:10.1126/sciadv.abd2781

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