Notch1 switches progenitor competence in inducing medulloblastoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34162555.
- Also identified by DOI 10.1126/sciadv.abd2781 and PMC identifier 8221631.
- Licence recorded as CC BY-NC.
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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 <i>MYC</i> and <i>Gfi1</i> in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b<sup>+</sup> cells are competent to initiate group 3 MB, and we observed that S100b<sup>+</sup> cells have higher levels of Notch1 pathway activity compared to Math1<sup>+</sup> cells. We found that additional activation of Notch1 in Math1<sup>+</sup> and Sox2<sup>+</sup> cells was sufficient to induce group 3 MB upon <i>MYC</i>/<i>Gfi1</i> expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.