Cited by 112Genetic Neurodegenerative DiseasesPluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanisms

Human Huntington's disease iPSC-derived cortical neurons display altered transcriptomics, morphology, and maturation

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Mehta, Shagun R., Tom, Colton M., Wang, Yizhou, Bresee, Catherine, Rushton, David, Mathkar, Pranav P., Tang, Jie, Mattis, Virginia B.·2018·Cell Reports

Abstract

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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Crossref · 10.1016/j.celrep.2018.09.076

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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
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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