ArticleCell stem cell2018
GFAP Mutations in Astrocytes Impair Oligodendrocyte Progenitor Proliferation and Myelination in an hiPSC Model of Alexander Disease.
Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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90 citing papers in PubMed, 133 citations in OpenAlex.
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- Revisiting oligodendrocytes in amyotrophic lateral sclerosis using human multicellular stem cell models.Trends in cell biology · 2026Review
- From insights to innovations: evaluating preclinical paradigms in demyelinating disease therapeutics.Lab animal · 2026Review
- Stage-specific CHI3L1/YKL-40 signaling controls generation of oligodendrocyte precursor cells through IL13Rα2-mediated ferroptosis.bioRxiv : the preprint server for biology · 2026Article
- Charting the transition from in vitro gliogenesis to the in vivo maturation of human glial progenitor cells transplanted into the hypomyelinated mouse brain.Nature communications · 2026Article
- MLC1 alteration in human iPSCs give rise to disease-like cellular vacuolation phenotype in the astrocyte lineage.Orphanet journal of rare diseases · 2026Article
- The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS.Acta neurologica Belgica · 2026Review
- Human iPSC-derived neural progenitor cells rescue motor function and brain pathology in symptomatic Canavan disease mice.Stem cell reports · 2026Article
- Unbiased bioinformatic and clinical analysis identifies glial fibrillary acidic protein as a potential biomarker in spinal muscular atrophy.Brain communications · 2026Article
- Targeting astrocytic CLC2(CLCN2) restores myelin regeneration through inhibition of SPP1/CD44 signaling pathway in leukoencephalopathy.Molecular psychiatry · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Article
- Targeting glioblastoma using oncolytic viruses delivered by human pluripotent stem cell-derived neural progenitor cells.Molecular therapy. Oncology · 2025Article
- Differential tropisms of old and new world hantaviruses influence virulence and developing host-directed antiviral candidates.PLoS pathogens · 2025Article
- CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer's disease.Science advances · 2025Article
- PepTune:ArXiv · 2025Article
- Current Development of iPSC-Based Modeling in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Human iPSC-derived microglial cells protect neurons from neurodegeneration in long-term cultured adhesion brain organoids.Communications biology · 2025Article
- Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease.CNS neuroscience & therapeutics · 2025Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Alexander disease (AxD) is a leukodystrophy that primarily affects astrocytes and is caused by mutations in the astrocytic filament gene GFAP. While astrocytes are thought to have important roles in controlling myelination, AxD animal models do not recapitulate critical myelination phenotypes and it is therefore not clear how AxD astrocytes contribute to leukodystrophy. Here, we show that AxD patient iPSC-derived astrocytes recapitulate key features of AxD pathology such as GFAP aggregation. Moreover, AxD astrocytes inhibit proliferation of human iPSC-derived oligodendrocyte progenitor cells (OPCs) in co-culture and reduce their myelination potential. CRISPR/Cas9-based correction of GFAP mutations reversed these phenotypes. Transcriptomic analyses of AxD astrocytes and postmortem brains identified CHI3L1 as a key mediator of AxD astrocyte-induced inhibition of OPC activity. Thus, this iPSC-based model of AxD not only recapitulates patient phenotypes not observed in animal models, but also reveals mechanisms underlying disease pathology and provides a platform for assessing therapeutic interventions.
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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.