ArticleCell reports2023
Astrocytic response mediated by the CLU risk allele inhibits OPC proliferation and myelination in a human iPSC model.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Interpretable deep neural network identifies robust biomarkers for diseases with mechanistic insights from omics data.Briefings in bioinformatics · 2026Article
- The complement system in Alzheimer's disease: evaluating biomarker potential in a complex neuroimmune context.Journal of neuroinflammation · 2026Review
- From insights to innovations: evaluating preclinical paradigms in demyelinating disease therapeutics.Lab animal · 2026Review
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- Single-cell polygenic risk scores dissect cellular and molecular heterogeneity of complex human diseases.Nature biotechnology · 2026Article
- Clusterin Regulates the Mechanisms of Neuroinflammation and Neuronal Circuit Impairment in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Screening biomarkers related to cholesterol metabolism in osteoarthritis based on transcriptomics.Scientific reports · 2025Article
- CRISPR/Cas9 and iPSC-Based Therapeutic Approaches in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Alzheimer's disease protective allele of Clusterin modulates neuronal excitability through lipid-droplet-mediated neuron-glia communication.Molecular neurodegeneration · 2025Article
- The Rise of Pluripotent Stem Cell-Derived Glia Models of Neuroinflammation.Neurology international · 2025Review
- Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease.Cell reports · 2024Article
- Pathologic TDP-43 downregulates myelin gene expression in the monkey brain.Brain pathology (Zurich, Switzerland) · 2024Article
- Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases.Nature communications · 2024Article
- Alzheimer's disease protective allele ofmedRxiv : the preprint server for health sciences · 2024Article
- Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications.Signal transduction and targeted therapy · 2024Review
- Comorbidity Genes of Alzheimer's Disease and Type 2 Diabetes Associated with Memory and Cognitive Function.International journal of molecular sciences · 2024Review
- Astrocyte ensheathment of calyx-forming axons of the auditory brainstem precedes accelerated expression of myelin genes and myelination by oligodendrocytes.The Journal of comparative neurology · 2024Article
- The Current Situation and Development Prospect of Whole-Genome Screening.International journal of molecular sciences · 2024Review
- White matter injury across neurodegenerative disease.Trends in neurosciences · 2024Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The C allele of rs11136000 variant in the clusterin (CLU) gene represents the third strongest known genetic risk factor for late-onset Alzheimer's disease. However, whether this single-nucleotide polymorphism (SNP) is functional and what the underlying mechanisms are remain unclear. In this study, the CLU rs11136000 SNP is identified as a functional variant by a small-scale CRISPR-Cas9 screen. Astrocytes derived from isogenic induced pluripotent stem cells (iPSCs) carrying the "C" or "T" allele of the CLU rs11136000 SNP exhibit different CLU expression levels. TAR DNA-binding protein-43 (TDP-43) preferentially binds to the "C" allele to promote CLU expression and exacerbate inflammation. The interferon response and CXCL10 expression are elevated in cytokine-treated C/C astrocytes, leading to inhibition of oligodendrocyte progenitor cell (OPC) proliferation and myelination. Accordingly, elevated CLU and CXCL10 but reduced myelin basic protein (MBP) expression are detected in human brains of C/C carriers. Our study uncovers a mechanism underlying reduced white matter integrity observed in the CLU rs11136000 risk "C" allele carriers.
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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.