ArticleScience advances2024
Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Trial
- Human iPSC-Derived Brain Organoids: A Disease-Oriented Evaluation of Modeling Fidelity.The European journal of neuroscience · 2026Review
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- REST deficiency and neurogenic-to-gliogenic shift in down syndrome human cerebral organoids.Molecular brain · 2026Article
- Inhibition of host N-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress.Nature communications · 2026Article
- Translating Pharmacology from Animal Models to Organoids: Advancing Predictive Human Biology in Drug Discovery.Stem cell reviews and reports · 2026Review
- Cerebrospinal fluid and frontal cortex TMPRSS2 and ACE2 protein levels differ in Down syndrome and Alzheimer's disease.Acta neuropathologica communications · 2026Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.American journal of human genetics · 2026Article
- Organoids in drug development: from predictive models to regulatory integration.Drug discovery today · 2026Review
- Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology.Stem cell research & therapy · 2026Review
- Relative biological effectiveness and neural stem cell fate in carbon ion-irradiated human brain organoids.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2026Article
- SARS-CoV-2 infection in hiPSC-derived neurons is cathepsin-dependent and causes differential accumulation of HIF1ɑ and phosphorylated tau.Molecular therapy. Nucleic acids · 2025Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.bioRxiv : the preprint server for biology · 2025Article
- Enhanced U-Net-Based Deep Learning Model for Automated Segmentation of Organoid Images.Bioengineering (Basel, Switzerland) · 2025Article
- Organoid Models to Study Human Infectious Diseases.Cell proliferation · 2025Review
- A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025Review
- The SARS-CoV-2 envelope PDZ binding motif acts as a virulence factor disrupting host's epithelial cell-cell junctions.Cellular & molecular biology letters · 2025Article
- Three-Dimensional-Bioprinted Embedded-Based Cerebral Organoids: An Alternative Approach for Mini-Brain In Vitro Modeling Beyond Conventional Generation Methods.Gels (Basel, Switzerland) · 2025Article
- Klotho overexpression protects human cortical neurons from β-amyloid induced neuronal toxicity.Molecular brain · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2-induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21-encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2-induced neuropathogenesis.
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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 Socratic graph.