ArticleDisease models & mechanisms2024
PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.
Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Paediatric Genetic Diseases: Models, Mechanisms and Therapies.Disease models & mechanisms · 2026Article
- Organoids as brain tumour models: bridging the translational gap.Disease models & mechanisms · 2026Review
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- Modeling medulloblastoma pathogenesis and treatment in human cerebellar organoids.Genes & development · 2026Article
- Stem Cell-Derived Organoids for Cancer Therapy: Precision Medicine and Drug Selection.International journal of molecular sciences · 2026Review
- Patient-derived complex organoids are a critical tool to understand and explore pediatric malignant brain tumors.Cancer metastasis reviews · 2026Review
- Article
- Medulloblastoma stem cell programs: Molecular roadmaps of disease progression.Developmental cell · 2026Review
- Generating cerebellar organoids from pluripotent stem cells.Disease models & mechanisms · 2026Review
- Modeling pediatric brain tumors with human stem cells.Frontiers in cellular neuroscience · 2026Review
- Advancing Medulloblastoma Treatment: Molecular Mechanisms, Drug Repurposing, and Precision Therapies.Molecular diagnosis & therapy · 2026Review
- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- Cerebellar organoids model cell type-specific FOXP2 expression during human cerebellar development.Disease models & mechanisms · 2025Article
- Conference Report: Cerebellar Development and Disease at Single-Cell Resolution.Cerebellum (London, England) · 2025Article
- Review
- Enhancing spinal cord injury repair through PTCH1-mediated neural progenitor cell differentiation induced by ion elemental-optimized layered double hydroxides.Materials today. Bio · 2025Article
- Arrested development: the dysfunctional life history of medulloblastoma.Genes & development · 2025Review
- Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Patched 1 (PTCH1) is the primary receptor for the sonic hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations in PTCH1 are associated with altered neuronal development and the malignant brain tumour medulloblastoma. As a result of differences between murine and human development, molecular and cellular perturbations that arise from human PTCH1 mutations remain poorly understood. Here, we used cerebellar organoids differentiated from human induced pluripotent stem cells combined with CRISPR/Cas9 gene editing to investigate the earliest molecular and cellular consequences of PTCH1 mutations on human cerebellar development. Our findings demonstrate that developmental mechanisms in cerebellar organoids reflect in vivo processes of regionalisation and SHH signalling, and offer new insights into early pathophysiological events of medulloblastoma tumorigenesis without the use of animal models.
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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.