ArticleNature cell biology2024
A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing.
Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- HnRNP C binding to invertedScience advances · 2026Article
- Medulloblastoma stem cell programs: Molecular roadmaps of disease progression.Developmental cell · 2026Review
- Alternative splicing in pediatric central nervous system tumors highlights oncofetal candidateNeuro-oncology pediatrics · 2026Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Engineering yeast peroxisome assembly enables the increased production of acetyl-CoA and its derived 5-deoxyflavonoids.Nature communications · 2025Article
- MOADE: a multimodal autoencoder for dissociating bulk multi-omics data.Genome biology · 2025Article
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein-protein interactions and regulates a stem cell splicing program. OTX2 can directly or indirectly bind RNA and this may be partially independent of its DNA regulatory functions. OTX2 controls a pro-tumorigenic splicing program that is mirrored in human cerebellar rhombic lip origins. Among the OTX2-regulated differentially spliced genes, PPHLN1 is expressed in the most primitive rhombic lip stem cells, and targeting PPHLN1 splicing reduces tumour growth and enhances survival in vivo. These findings identify OTX2-mediated alternative splicing as a major determinant of cell fate decisions that drive group 3 MB progression.
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Registered trials
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