ArticleScientific reports2018
Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- CRISPR/Cas9-mediated gene correction of Wilson disease H1069Q point mutation in patient-specific induced pluripotent stem cells.Gene therapy · 2026Article
- ATPase copper transporting beta contributes to cisplatin resistance as a regulatory factor of extracellular vesicles in head and neck squamous cell carcinoma.Cancer gene therapy · 2026Article
- Ligase-mediated programmable genomic integration (L-PGI).Nature communications · 2025Article
- Evaluation of the Relationship Between Neurologic Manifestations and Genetic Mutations in Wilson's Disease with Next-Generation Sequencing.Diagnostics (Basel, Switzerland) · 2025Article
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.Stem cell reviews and reports · 2025Review
- The role of copper dysregulation in Wilson disease: an expert opinion.Frontiers in medicine · 2025Review
- The physiological and pathophysiological roles of copper in the nervous system.The European journal of neuroscience · 2024Review
- A new Caenorhabditis elegans model to study copper toxicity in Wilson disease.Traffic (Copenhagen, Denmark) · 2024Article
- Experimental evidence and clinical implications of Warburg effect in the skeletal muscle of Fabry disease.iScience · 2023Article
- Missing heritability of Wilson disease: a search for the uncharacterized mutations.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- A Century of Progress on Wilson Disease and the Enduring Challenges of Genetics, Diagnosis, and Treatment.Biomedicines · 2023Article
- From a Single Cell to a Whole Human Liver: Disease Modeling and Transplantation.Seminars in liver disease · 2022Article
- Retinoids rescue ceruloplasmin secretion and alleviate oxidative stress in Wilson's disease-specific hepatocytes.Human molecular genetics · 2022Article
- Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells.Genes · 2022Review
- Induction of Bile Canaliculi-Forming Hepatocytes from Human Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- From Cells to Organs: The Present and Future of Regenerative Medicine.Advances in experimental medicine and biology · 2022Review
- Review
- Synthetic human livers for modeling metabolic diseases.Current opinion in gastroenterology · 2021Review
- Therapeutic strategies in Wilson disease: pathophysiology and mode of action.Annals of translational medicine · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
H1069Q substitution represents the most frequent mutation of the copper transporter ATP7B causing Wilson disease in Caucasian population. ATP7B localizes to the Golgi complex in hepatocytes but moves in response to copper overload to the endo-lysosomal compartment to support copper excretion via bile canaliculi. In heterologous or hepatoma-derived cell lines, overexpressed ATP7B-H1069Q is strongly retained in the ER and fails to move to the post-Golgi sites, resulting in toxic copper accumulation. However, this pathogenic mechanism has never been tested in patients' hepatocytes, while animal models recapitulating this form of WD are still lacking. To reach this goal, we have reprogrammed skin fibroblasts of homozygous ATP7B-H1069Q patients into induced pluripotent stem cells and differentiated them into hepatocyte-like cells. Surprisingly, in HLCs we found one third of ATP7B-H1069Q localized in the Golgi complex and able to move to the endo-lysosomal compartment upon copper stimulation. However, despite normal mRNA levels, the expression of the mutant protein was only 20% compared to the control because of endoplasmic reticulum-associated degradation. These results pinpoint rapid degradation as the major cause for loss of ATP7B function in H1069Q patients, and thus as the primary target for designing therapeutic strategies to rescue ATP7B-H1069Q function.
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