First Author | Ballabio C | Year | 2021 |
Journal | Sci Adv | Volume | 7 |
Issue | 26 | PubMed ID | 34162555 |
Mgi Jnum | J:314917 | Mgi Id | MGI:6828923 |
Doi | 10.1126/sciadv.abd2781 | Citation | Ballabio C, et al. (2021) Notch1 switches progenitor competence in inducing medulloblastoma. Sci Adv 7(26) |
abstractText | 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. |