ArticleMolecular brain2021
Modeling PTEN overexpression-induced microcephaly in human brain organoids.
Article in Molecular brain, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 37 citations in OpenAlex.
- Pathological Priming and Developmental Heterochrony as Organizing Concepts in Human iPSC Models of Autism Spectrum Disorder.Molecular neurobiology · 2026Review
- Divergence between neural and retinal lineage specification during human brain development by signal transduction.Journal of advanced research · 2026Article
- Inhibition of PTEN nuclear translocation by peptide Tat-K13 attenuates p-JUN-SESN2-AMPK-dependent autophagy and enhances neurological recovery after neonatal hypoxic-ischemic brain damage.Cell & bioscience · 2026Article
- Epilepsy-associated FOXJ3 variants link a transcriptional program of the PTEN-mTOR pathway to neuronal specification and cortical lamination.Nature communications · 2026Article
- PTEN variant and genetic backgrounds combine to modify cerebellar neuronal differentiation in autism spectrum disorder.Human molecular genetics · 2026Article
- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- LncRNA CISTR-ACT regulates cell size in human and mouse by guiding FOSL2.Nature communications · 2025Article
- A phenotypic brain organoid atlas and biobank for neurodevelopmental disorders.Cell stem cell · 2025Article
- Cellular Characterization and Neural Electrophysiology in Cerebral Organoid Models of Neurological Disorders.Aging and disease · 2025Review
- Exploring Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) as a Potential Therapeutic Target for Cardiac Hypertrophy.ACS pharmacology & translational science · 2025Review
- Review
- Human Brain Organoids: Development and Applications.Journal of microbiology and biotechnology · 2025Review
- Modelling human brain development and disease with organoids.Nature reviews. Molecular cell biology · 2025Review
- Cerebral organoid research for pediatric patients with neurological disorders.Clinical and experimental pediatrics · 2025Article
- Autophagy controls neuronal differentiation by regulating the WNT-DVL signaling pathway.Autophagy · 2025Article
- Toxicity assessment using neural organoids: innovative approaches and challenges.Toxicological research · 2025Review
- Brain organoids: a new paradigm for studying human neuropsychiatric disorders.Frontiers in neuroscience · 2025Review
- Assessment of Expression of lncRNAs in Autistic Patients.Journal of molecular neuroscience : MN · 2024Article
- Morphogenetic Designs, and Disease Models in Central Nervous System Organoids.International journal of molecular sciences · 2024Review
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The phosphatase and tensin homolog (PTEN) protein, encoded by the PTEN gene on chromosome 10, is a negative regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway. Loss of PTEN has been linked to an array of human diseases, including neurodevelopmental disorders such as macrocephaly and autism. However, it remains unknown whether increased dosage of PTEN can lead to human disease. A recent human genetics study identifies chromosome 10 microduplication encompassing PTEN in patients with microcephaly. Here we generated a human brain organoid model of increased PTEN dosage. We showed that mild PTEN overexpression led to reduced neural precursor proliferation, premature neuronal differentiation, and the formation of significantly smaller brain organoids. PTEN overexpression resulted in decreased AKT activation, and treatment of wild-type organoids with an AKT inhibitor recapitulated the reduced brain organoid growth phenotypes. Together, our findings provide functional evidence that PTEN is a dosage-sensitive gene that regulates human neurodevelopment, and that increased PTEN dosage in brain organoids results in microcephaly-like phenotypes.
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