Human Huntington's disease iPSC-derived cortical neurons display altered transcriptomics, morphology, and maturation
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Huntington's disease (HD) is a neurodegenerative disease caused by an expanded CAG repeat in the Huntingtin (HTT) gene. Induced pluripotent stem cell (iPSC) models of HD provide an opportunity to study the mechanisms underlying disease pathology in disease-relevant patient tissues. Murine studies have demonstrated that HTT is intricately involved in corticogenesis. However, the effect of mutant Hungtintin (mtHTT) in human corticogenesis has not yet been thoroughly explored. This examination is critical, due to inherent differences in cortical development and timing between humans and mice. We therefore differentiated HD and non-diseased iPSCs into functional cortical neurons. While HD patient iPSCs can successfully differentiate toward a cortical fate in culture, the resulting neurons display altered transcriptomics, morphological and functional phenotypes indicative of altered corticogenesis in HD.
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The increased white matter and neuropil density alongside striatal volume loss in R6/2 mice might arise from impaired neurite outgrowth or disrupted synapses in Huntington's disease.
“the enhanced white matter and neuropil density coincident with striatal volume loss in R6/2 mice may stem from impaired neurite outgrowth”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Mehta et al., 2018
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- Authors
- Mehta, S. R., Tom, C. M., Wang, Y., Bresee, C., Rushton, D., Mathkar, P. P., Tang, J., & Mattis, V. B.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Mattis, Virginia B.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 25
- Issue
- 4
- Pages
- 1081-1096.e6
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2897213229
- Cited by
- 112
- References
- 70
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 12 · 2023: 8 · 2022: 16 · 2021: 18 · 2020: 21 · 2019: 11
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- CTSI (UL1TR001881-01)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Huntington's disease, induced pluripotent stem cells, cortical neurons, cortical development, mutant huntingtin, CAG repeat expansion, transcriptomics, neuronal morphology, neuronal maturation, iPSC-derived neurons
- MeSH terms
- Cell Differentiation, Cells, Cultured, Cerebral Cortex, Humans, Huntington Disease, Neurons, Phenotype, Neurites, Cell Shape, Gene Regulatory Networks, Induced Pluripotent Stem Cells, Transcriptome
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