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In vivo modeling of human neuron dynamics and Down syndrome
Open accessAbstract
Development of human brain neurons: The earliest stages of human brain development are very difficult to monitor, but using induced pluripotent stem cells (iPSCs) can help to elucidate the process. Real et al. transplanted neural progenitors derived from human iPSCs into the brains of adult mice. They used intravital imaging to visualize how resulting neurons grew and connected. The human cells produced neurons that integrated and developed synaptic networks with oscillatory activity. Dendritic pruning was observed and involved a process of branch retraction, not degeneration. Cells derived from individuals with Down syndrome, upon transplantation into the mouse brain, produced neurons that grew normally but showed reduced dendritic spine turnover and less network activity. Science , this issue p. eaau1810
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“This contrasts with recent findings in PSC-derived human cortical neurons transplanted as bulk cell populations, which displayed rapid dendritic spine turnover throughout the experiment (spine half-life <4 days versus 2 weeks at 3–4 months), and reached very limited levels of synaptic connectivity with the host brain (Real et al., 2018).”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Real et al., 2018
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“Fewer trisomic grafts exhibited bursting activity and those that did had reduced bursting frequency (Real et al., 2018).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Real et al., 2018
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“These activity changes indicate that it may be alterations in circuitry rather than changes in intrinsic neuronal properties that may be responsible for altered neuronal activity.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Real et al., 2018
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“A recent study using in vivo imaging showed limited synaptic integration of human cortical pyramidal neurons in the mouse cortex”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Real et al., 2018
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“More recently, xenografts of human iPSC-derived neurons into mouse brain revealed that, although both control neurons and T21 neurons can successfully incorporate into the mouse brain by forming synapses with the surrounding mouse neurons, T21 neurons exhibit reduced network activity relative to control neurons133.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [133]
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“Moreover, neurons generated from iPSCs derived from individuals with DS have little to no capacity for either LTP or LTD in vitro132, and when transplanted into the mouse brain, these neurons have reduced structural plasticity relative to controls133.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [133]
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“A novel study where NPCs and neurons derived from iPSCs were engrafted into mouse cortex and allowed to mature found an increase in spine density in the trisomic neurons compared to euploid controls (Real et al., 2018).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Real et al., 2018
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“The spines on the trisomic neurons also appeared to be more stable, with less turnover observed in trisomic neurons compared to euploid.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Real et al., 2018
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“Recent studies using complementary mouse models of DS, including Ts65Dn, Ts2Cje, Tc1, and Dp16 mice, reported an activated phenotype in microglia cells during brain development, as evidenced by functional morphological alterations and elevated pro-inflammatory cytokines, accompanied by a reduction of neuronal dendritic spines.26,27,28,29”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [29]
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Metadata
- Authors
- Real, R., Peter, M., Trabalza, A., Khan, S., Smith, M. A., Dopp, J., Barnes, S. J., Momoh, A., Strano, A., Volpi, E., Knott, G., Livesey, F. J., & De Paola, V.
- Affiliations
- Universidade do Porto (PT)
- University of Cambridge (GB)
- Imperial College London (GB)
- UK Dementia Research Institute (GB)
- University of Westminster (GB)
- École Polytechnique Fédérale de Lausanne (CH)
- Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
- Corresponding author
- Real, Raquel
- Peter, Manuel
- Trabalza, Antonio
- Livesey, Frederick J.
- ORCID
- Venue
- Science
- Published
- 2018-11-16
- Volume
- 362
- Issue
- 6416
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6570619
- OpenAlex
- W2896561023
- Cited by
- 120
- References
- 60
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 16 · 2022: 22 · 2021: 15 · 2020: 24 · 2019: 10 · 2018: 4
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- WestminsterResearch (University of Westminster) (acceptedVersion)
- Lirias (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Spiral (Imperial College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- Down syndrome, in vivo imaging, synaptic stability, neural oscillations, cortical development, patient-specific modeling
- MeSH terms
- Animals, Axons, Cerebral Cortex, Down Syndrome, Humans, Models, Biological, Neuroglia, Neuronal Plasticity, Neurons, Synapses, Mice, SCID, Microscopy, Fluorescence, Multiphoton, Mice, Neurogenesis, Induced Pluripotent Stem Cells, Neural Stem Cells, Single-Cell Analysis, Neuroimaging
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