ArticleHuman molecular genetics2018
Patient iPSC-derived neural stem cells exhibit phenotypes in concordance with the clinical severity of mucopolysaccharidosis I.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Short-lived Niemann-Pick type C mice with accelerated brain aging as a novel model for Alzheimer's disease research.Neural regeneration research · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Neuroinflammation as a Novel Therapeutic Frontier for Sanfilippo Syndrome.Children (Basel, Switzerland) · 2025Review
- Induced Pluripotent Stem Cells for the Treatment of Lysosomal Storage Disorders.Journal of inherited metabolic disease · 2025Review
- Establishment of a Human iPSC Line from Mucolipidosis Type II That Expresses the Key Markers of the Disease.International journal of molecular sciences · 2025Article
- Systematic identification of cancer pathways and potential drugs for intervention through multi-omics analysis.The pharmacogenomics journal · 2025Article
- Unifying biology of neurodegeneration in lysosomal storage diseases.Journal of inherited metabolic disease · 2025Review
- Review
- Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses.Biomedicines · 2023Review
- iPS-derived neural stem cells for disease modeling and evaluation of therapeutics for mucopolysaccharidosis type II.Experimental cell research · 2022Article
- Innate Immunity in Mucopolysaccharide Diseases.International journal of molecular sciences · 2022Review
- Impaired neural differentiation of MPS IIIA patient induced pluripotent stem cell-derived neural progenitor cells.Molecular genetics and metabolism reports · 2021Article
- Disease modeling for Mucopolysaccharidosis type IIIB using patient derived induced pluripotent stem cells.Experimental cell research · 2021Article
- Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells.International journal of molecular sciences · 2021Article
- The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower.Stem cell reviews and reports · 2021Review
- Enlightenment of Growth Plate Regeneration Based on Cartilage Repair Theory: A Review.Frontiers in bioengineering and biotechnology · 2021Review
- Article
- Soy Protein Nanofiber Scaffolds for Uniform Maturation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium.Tissue engineering. Part C, Methods · 2020Article
- Generation and characterization of human induced pluripotent stem cells (iPSCs) from hand osteoarthritis patient-derived fibroblasts.Scientific reports · 2020Article
- Mucopolysaccharidosis and Autophagy: Controversies on the Contribution of the Process to the Pathogenesis and Possible Therapeutic Applications.Neuromolecular medicine · 2020Review
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5 authors.
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Abstract
Mucopolysaccharidosis type I (MPS I) is caused by deficiency of α-l-iduronidase (IDUA), a lysosomal enzyme involved in the breakdown and recycling of glycosaminoglycans (GAGs). Although enzyme replacement therapy is available, the efficacy of the treatment for neuropathic manifestations is limited. To facilitate drug discovery and model disease pathophysiology, we generated neural stem cells (NSCs) from MPS I patient-derived induced pluripotent stem cells (iPSCs). The NSCs exhibited characteristic disease phenotypes with deficiency of IDUA, accumulation of GAGs and enlargement of lysosomes, in agreement with the severity of clinical subgroups of MPS I. Transcriptome profiling of NSCs revealed 429 genes that demonstrated a more extensive change in expression in the most severe Hurler syndrome subgroup compared to the intermediate Hurler-Scheie or the least severe Scheie syndrome subgroups. Clustering and pathway analysis revealed high concordance of the severity of neurological defects with marked dysregulation of GAG biosynthesis, GAG degradation, lysosomal function and autophagy. Gene ontology (GO) analysis identified a dramatic upregulation of the autophagy pathway, especially in the Hurler syndrome subgroup. We conclude that GAG accumulation in the patient-derived cells disrupts lysosomal homeostasis, affecting multiple related cellular pathways in response to IDUA deficiency. These dysregulated processes likely lead to enhanced autophagy and progressively severe disease states. Our study provides potentially useful targets for clinical biomarker development, disease diagnosis and prognosis, and drug discovery.
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