Notch1 switches progenitor competence in inducing medulloblastoma - Sorbonne Université
Journal Articles Science Advances Year : 2021

Notch1 switches progenitor competence in inducing medulloblastoma

Abstract

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.
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Dates and versions

hal-03272112 , version 1 (28-06-2021)

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Claudio Ballabio, Matteo Gianesello, Chiara Lago, Konstantin Okonechnikov, Marica Anderle, et al.. Notch1 switches progenitor competence in inducing medulloblastoma. Science Advances , 2021, 7 (26), pp.eabd2781. ⟨10.1126/sciadv.abd2781⟩. ⟨hal-03272112⟩
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