ArticleThe Journal of experimental medicine2021
Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- Sox9 regulation of hexokinase 1 controls neuroinflammatory astrocyte subtypes in a rat model of neuropathic pain.Nature communications · 2025Article
- OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma.Nature communications · 2025Article
- High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.Cell reports. Medicine · 2025Article
- MAP4 kinase-regulated reduced CLSTN1 expression in medulloblastoma is associated with increased invasiveness.Scientific reports · 2025Article
- Old players and new insights: unraveling the role of RNA-binding proteins in brain tumors.Theranostics · 2025Review
- Thyroid hormone suppresses medulloblastoma progression through promoting terminal differentiation of tumor cells.Cancer cell · 2024Article
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage.Nature communications · 2024Article
- Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2.Brain pathology (Zurich, Switzerland) · 2024Article
- A preliminary study on the mechanism of VASH2 in childhood medulloblastoma.Scientific reports · 2023Article
- Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.Nature cell biology · 2023Article
- Spatial transcriptomic analysis of Sonic hedgehog medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition.Genome medicine · 2023Article
- IGFBP2 promotes proliferation and cell migration through STAT3 signaling in Sonic hedgehog medulloblastoma.Acta neuropathologica communications · 2023Article
- Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses.Acta neuropathologica communications · 2023Article
- Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma.Cancer research · 2022Article
- The Tumor Microenvironment of Medulloblastoma: An Intricate Multicellular Network with Therapeutic Potential.Cancers · 2022Review
- Complement C3a activates astrocytes to promote medulloblastoma progression through TNF-α.Journal of neuroinflammation · 2022Article
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.