ArticleCommunications biology2021
Cryptic developmental events determine medulloblastoma radiosensitivity and cellular heterogeneity without altering transcriptomic profile.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Myeloid compartment reprogramming through nanoparticle-delivered resiquimod blocks paracrine growth support and activates phagocytosis to slow tumor progression in endogenous mouse medulloblastoma and diffuse midline glioma models.bioRxiv : the preprint server for biology · 2026Article
- Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179.Nature communications · 2025Article
- Single-Cell Chromatin Accessibility Analysis Reveals Subgroup-Specific TF-NTR Regulatory Circuits in Medulloblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Review
- Chronic AMPK inactivation slows SHH medulloblastoma progression by inhibiting mTORC1 signaling and depleting tumor stem cells.iScience · 2023Article
- Pediatric Brain Tumours: Lessons from the Immune Microenvironment.Current oncology (Toronto, Ont.) · 2023Review
- IGFBP2 promotes proliferation and cell migration through STAT3 signaling in Sonic hedgehog medulloblastoma.Acta neuropathologica communications · 2023Article
- PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth.Acta neuropathologica communications · 2023Article
- OLIG2 Is a Determinant for the Relapse of MYC-Amplified Medulloblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Enhancing CDK4/6 inhibitor therapy for medulloblastoma using nanoparticle delivery and scRNA-seq-guided combination with sapanisertib.Science advances · 2022Article
- Poly(2-oxazoline) nanoparticle delivery enhances the therapeutic potential of vismodegib for medulloblastoma by improving CNS pharmacokinetics and reducing systemic toxicity.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
- Pediatric Tumors as Disorders of Development: The Case for In Vitro Modeling Based on Human Stem Cells.Cancer control : journal of the Moffitt Cancer CenterReview
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
It is unclear why medulloblastoma patients receiving similar treatments experience different outcomes. Transcriptomic profiling identified subgroups with different prognoses, but in each subgroup, individuals remain at risk of incurable recurrence. To investigate why similar-appearing tumors produce variable outcomes, we analyzed medulloblastomas triggered in transgenic mice by a common driver mutation expressed at different points in brain development. We genetically engineered mice to express oncogenic SmoM2, starting in multipotent glio-neuronal stem cells, or committed neural progenitors. Both groups developed medulloblastomas with similar transcriptomic profiles. We compared medulloblastoma progression, radiosensitivity, and cellular heterogeneity, determined by single-cell transcriptomic analysis (scRNA-seq). Stem cell-triggered medulloblastomas progressed faster, contained more OLIG2-expressing stem-like cells, and consistently showed radioresistance. In contrast, progenitor-triggered MBs progressed slower, down-regulated stem-like cells and were curable with radiation. Progenitor-triggered medulloblastomas also contained more diverse stromal populations, with more Ccr2+ macrophages and fewer Igf1+ microglia, indicating that developmental events affected the subsequent tumor microenvironment. Reduced mTORC1 activity in M-Smo tumors suggests that differential Igf1 contributed to differences in phenotype. Developmental events in tumorigenesis that were obscure in transcriptomic profiles thus remained cryptic determinants of tumor composition and outcome. Precise understanding of medulloblastoma pathogenesis and prognosis requires supplementing transcriptomic/methylomic studies with analyses that resolve cellular heterogeneity.
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