Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder
Open accessAbstract
A deletion or duplication in the 16p11.2 region is associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. In addition to clinical characteristics, carriers of the 16p11.2 copy-number variant (CNV) manifest opposing neuroanatomical phenotypes-e.g., macrocephaly in deletion carriers (16pdel) and microcephaly in duplication carriers (16pdup). Using fibroblasts obtained from 16pdel and 16pdup carriers, we generated induced pluripotent stem cells (iPSCs) and differentiated them into neurons to identify causal cellular mechanisms underlying neurobiological phenotypes. Our study revealed increased soma size and dendrite length in 16pdel neurons and reduced neuronal size and dendrite length in 16pdup neurons. The functional properties of iPSC-derived neurons corroborated aspects of these contrasting morphological differences that may underlie brain size. Interestingly, both 16pdel and 16pdup neurons displayed reduced synaptic density, suggesting that distinct mechanisms may underlie brain size and neuronal connectivity at this locus.
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Human iPSC-derived neurons from 16p11.2 deletion/duplication carriers display increased soma size/dendrite length in deletion neurons and reduced size/dendrite length in duplication neurons.
“Human induced pluripotent stem cell (iPSC)-derived neurons from 16p11.2 deletion/duplication carriers display corresponding features, with increased soma size/dendrite length in 16p11.2 deletion neurons, and reduced size/dendrite length in duplication neurons [77].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [77]
Cellular models of reciprocal 16p11.2 deletions and duplications recapitulate mirror effects on cell proliferation and reveal mirror effects on synaptic density.
“Cellular models of reciprocal deletions and duplications of 16p11.2 recapitulate mirror effects on cell proliferation and reveal mirror effects on synaptic density (Deshpande et al., 2017).”
From Getting to the cores of autism (2019) · cites this paper as Deshpande et al., 2017
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“2 recapitulate mirror effects on cell proliferation and reveal mirror effects on synaptic density (Deshpande et al., 2017).”
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Autism spectrum disorder and various mechanisms behind it
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Investigation of Schizophrenia with Human Induced Pluripotent Stem Cells
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Atypical neural variability in carriers of 16p11.2 copy number variants
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Patient Brain Organoids Identify a Link between the 16p11.2 Copy Number Variant and the RBFOX1 Gene
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Analysis of neuronal activity impairment in iPSC-derived neurons from idiopathic autism patients
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- Authors
- Deshpande, A., Yadav, S., Dao, D. Q., Wu, Z.-Y., Hokanson, K. C., Cahill, M. K., Wiita, A. P., Jan, Y.-N., Ullian, E. M., & Weiss, L. A.
- Affiliations
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Weiss, Lauren A.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 21
- Issue
- 10
- Pages
- 2678-2687
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5730067
- OpenAlex
- W2775613815
- Cited by
- 151
- References
- 48
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 15 · 2023: 15 · 2022: 15 · 2021: 29 · 2020: 19 · 2019: 20 · 2018: 8
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Simons Foundation (SFARI 345471)
- NIH (DP2 OD007449, R21 MH105745, 5K99MH108648-02, EY007120)
- CIRM Bridges
- Autism Speaks Meixner Postdoctoral Fellowship
- Research to Prevent Blindness (EY002162)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- autism spectrum disorder, 16p11.2 deletion, 16p11.2 duplication, iPSC-derived neurons, neuronal soma size, dendritic length, brain size, synaptic density, neuronal connectivity, macrocephaly, microcephaly, neurodevelopmental disorders
- MeSH terms
- Autism Spectrum Disorder, Autistic Disorder, Cell Differentiation, Chromosome Deletion, Chromosomes, Human, Pair 16, Humans, Microcephaly, Models, Genetic, Neurons, DNA Copy Number Variations, Induced Pluripotent Stem Cells, Megalencephaly, Chromosome Duplication
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