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Updated: Feb 9, 2026
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
Mouse medulloblastoma driven by CRISPR activation of cellular Myc
BaoHan T Vo1, Jin Ah Kwon1,2, Chunliang Li1
1Department of Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Abstract:
MYC-driven Group 3 (G3) medulloblastoma (MB) is the most aggressive of four molecular subgroups classified by transcriptome, genomic landscape and clinical outcomes. Mouse models that recapitulate human G3 MB all rely on retroviral vector-induced Myc expression driven by viral regulatory elements (Retro-Myc tumors). We used nuclease-deficient CRISPR/dCas9-based gene activation with combinatorial single guide RNAs (sgRNAs) to enforce transcription of endogenous Myc in Trp53-null neurospheres that were orthotopically transplanted into the brains of naïve animals. Three combined sgRNAs linked to dCas9-VP160 induced cellular Myc expression and large cell anaplastic MBs (CRISPR-Myc tumors) which recapitulated the molecular characteristics of mouse and human G3 MBs. The BET inhibitor JQ1 suppressed MYC expression in a human G3 MB cell line (HD-MB03) and CRISPR-Myc, but not in Retro-Myc MBs. This G3 MB mouse model in which Myc expression is regulated by its own promoter will facilitate pre-clinical studies with drugs that regulate Myc transcription.
Insights
Researchers developed a new mouse model for aggressive Group 3 medulloblastoma (MB) using CRISPR gene activation. This model, unlike previous ones, regulates Myc expression naturally, enabling better pre-clinical drug testing for this challenging brain tumor.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Group 3 medulloblastoma (G3 MB) is the most aggressive subtype.
- Existing mouse models (Retro-Myc) use viral elements to drive Myc, not reflecting natural gene regulation.
Purpose of the Study:
- To develop a novel G3 MB mouse model with endogenous Myc activation.
- To create a platform for pre-clinical testing of therapies targeting Myc transcription.
Main Methods:
- Utilized CRISPR/dCas9-based gene activation with sgRNAs to induce endogenous Myc expression in Trp53-null neurospheres.
- Orthotopically transplanted engineered neurospheres into mouse brains to establish tumors.
- Assessed tumor characteristics and response to BET inhibitor JQ1.
Main Results:
- CRISPR-Myc tumors recapitulated molecular features of human G3 MB.
- Endogenous Myc activation led to large cell anaplastic medulloblastomas.
- JQ1 suppressed MYC in CRISPR-Myc tumors but not in Retro-Myc tumors.
Conclusions:
- A novel G3 MB mouse model with endogenous Myc regulation was established.
- This model accurately mimics human G3 MB molecular profiles.
- The model is suitable for pre-clinical evaluation of drugs targeting Myc transcription.
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