ArticleThe Journal of clinical investigation2021
DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Article
- MECP2Science China. Life sciences · 2026Article
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- Abnormal neuronal and synaptic morphology in Down syndrome brains reproduces in human isogenic cellular models.Cell death & disease · 2026Article
- Aberrant chromatin remodeling influences human neural cell fate change in Trisomy 21.bioRxiv : the preprint server for biology · 2026Article
- REST deficiency and neurogenic-to-gliogenic shift in down syndrome human cerebral organoids.Molecular brain · 2026Article
- A Novel Acetylcholine Nanosensor for Single Vesicle Storage and Sub-Quantal Exocytosis in Living Neurons and Organoids.Angewandte Chemie (International ed. in English) · 2026Article
- Multi-Omics Reveals Dysregulated Neurotransmitter Systems in Aging and CNS Disorders.Aging cell · 2026Article
- FABP7 controls radial glial scaffold stability during human cortical development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Single-cell atlas of the developing Down syndrome brain cortex.Nature medicine · 2026Article
- Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology.Stem cell research & therapy · 2026Review
- Diagnostic Value of Choroid Plexus-to-Lateral Ventricle Volume Ratio (CLVVR) in First-Trimester Screening (11-13⁺International journal of general medicine · 2026Article
- Neural Organoids Protect Engineered Heart Tissues From Glucolipotoxicity by Transferring Versican in a Co-Culture System.Cell proliferation · 2026Article
- PANoptosis-based HNSCPAN-index predicts prognosis and reveals DSCAM as a therapeutic target in head and neck squamous cell carcinoma.PloS one · 2026Article
- PAK1 (p21-Activated Kinase 1) and Its Role in Neurodevelopmental Disorders-New Case Report and a Comprehensive Review.International journal of molecular sciences · 2025Review
- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- Mid-gestational cell-type-specific transcriptomic signatures in the prefrontal and superior temporal cortex in Down syndrome.Nature communications · 2025Article
- A neuroimmune cerebral assembloid model to study the pathophysiology of familial Alzheimer's disease.Journal of neuroinflammation · 2025Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Down syndrome (DS), caused by trisomy of chromosome 21, occurs in 1 of every 800 live births. Early defects in cortical development likely account for the cognitive impairments in DS, although the underlying molecular mechanism remains elusive. Here, we performed histological assays and unbiased single-cell RNA-Seq (scRNA-Seq) analysis on cerebral organoids derived from 4 euploid cell lines and from induced pluripotent stem cells (iPSCs) from 3 individuals with trisomy 21 to explore cell-type-specific abnormalities associated with DS during early brain development. We found that neurogenesis was significantly affected, given the diminished proliferation and decreased expression of layer II and IV markers in cortical neurons in the subcortical regions; this may have been responsible for the reduced size of the organoids. Furthermore, suppression of the DSCAM/PAK1 pathway, which showed enhanced activity in DS, using CRISPR/Cas9, CRISPR interference (CRISPRi), or small-molecule inhibitor treatment reversed abnormal neurogenesis, thereby increasing the size of organoids derived from DS iPSCs. Our study demonstrates that 3D cortical organoids developed in vitro are a valuable model of DS and provide a direct link between dysregulation of the DSCAM/PAK1 pathway and developmental brain defects in DS.
Indexed as
Identifiers
What OpenQuestion holds
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.