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Status |
Public on Jun 30, 2021 |
Title |
Notch1 switches progenitor competence in inducing medulloblastoma |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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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. Interestingly, we found that additional activation of Notch1 in Math1+ and Sox2+ cells was sufficient to induce Group 3 MB upon MYC/Gfi1 expression. Taken together, our data suggest that the Notch1 pathway plays a critical role in Group 3 MB initiation.
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Overall design |
RNA-sequencing profiles of medulloblastoma samples induced by N1ICD+MYC/Gfi1 (in Math1+ cells) and MYC/Gfi1 (in S100b+ cells) compared with previously published Group 3 MB mouse models (MYC/Gfi1, MYC/Otx2)
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Contributor(s) |
Ballabio C, Gianesello M, Okonechnikov K, Tiberi L |
Citation(s) |
34162555 |
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Submission date |
May 05, 2021 |
Last update date |
Jul 02, 2021 |
Contact name |
Luca Tiberi |
E-mail(s) |
Luca.tiberi@unitn.it
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Phone |
+390461285356
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Organization name |
University of Trento
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Department |
Department of Cellular, Computational and Integrative Biology - CIBIO
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Lab |
Armenise-Harvard Laboratory of Brain Disorders and Cancer
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Street address |
via Sommarive, 9
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City |
Trento |
State/province |
TN |
ZIP/Postal code |
38123 |
Country |
Italy |
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Platforms (2) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (11)
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GSM5282388 |
Medulloblastoma MYC-Otx2_rep2 |
GSM5282389 |
Medulloblastoma MYC-Otx2_rep3 |
GSM5282390 |
Medulloblastoma MYC-Gfi1 (in S100b+ cells)_rep1 |
GSM5282391 |
Medulloblastoma MYC-Gfi1 (in S100b+ cells)_rep2 |
GSM5282392 |
Medulloblastoma MYC-Gfi1 (in S100b+ cells)_rep3 |
GSM5282393 |
Medulloblastoma MYC-Gfi1-N1ICD (in Math1+ cells)_rep1 |
GSM5282394 |
Medulloblastoma MYC-Gfi1-N1ICD (in Math1+ cells)_rep2 |
GSM5282395 |
Medulloblastoma MYC-Gfi1-N1ICD (in Math1+ cells)_rep3 |
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Relations |
BioProject |
PRJNA727475 |
SRA |
SRP318533 |