ArticleThe Journal of clinical investigation2024
Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Lentiviral-mediated gene complementation to rescue pathogenic ABCA3 variants.American journal of respiratory cell and molecular biology · 2026Article
- Respiratory Outcomes in Children With Neonatal Respiratory Distress Syndrome and Monoallelic ABCA3 Variants.Pediatric pulmonology · 2026Article
- Macrophages orchestrate antiviral defense and epithelial repair in a human iPSC-derived alveolar air-liquid interface.JCI insight · 2026Article
- Long isoforms of the COPD risk gene FAM13A orchestrate human lung epithelial development.American journal of respiratory cell and molecular biology · 2026Article
- AT2-intrinsic Z-AAT expression drives conserved inflammatory and proteotoxic stress responses and predisposes to emphysema.bioRxiv : the preprint server for biology · 2026Article
- Review
- Biallelic LAMP3 variants in 5 families with interstitial lung disease: Evidence of a disease-gene association.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Lipid droplet-mitochondria contact sites as druggable spatial-pharmacology targets in respiratory disease: cross-cell-type mechanisms and translational strategies.Frontiers in cell and developmental biology · 2026Review
- GDF11-secreting cell transplant efficiently ameliorates age-related pulmonary fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lentiviral-mediated gene complementation rescues pathogenicbioRxiv : the preprint server for biology · 2025Article
- Article
- Evaluating the Use of iPSC-Derived Models in Understanding the Pathogenesis of Childhood Interstitial Lung Disease.Pediatric pulmonology · 2025Review
- THERAPIES FOR NEONATAL DISEASES OF THE SURFACTANT SYSTEM.Transactions of the American Clinical and Climatological Association · 2025Review
- Clinical and research innovations in childhood interstitial lung disease (chILD).Pediatric pulmonology · 2024Article
- Building a human lung from pluripotent stem cells to model respiratory viral infections.Respiratory research · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in ATP-binding cassette A3 (ABCA3), a phospholipid transporter critical for surfactant homeostasis in pulmonary alveolar type II epithelial cells (AEC2s), are the most common genetic causes of childhood interstitial lung disease (chILD). Treatments for patients with pathological variants of ABCA3 mutations are limited, in part due to a lack of understanding of disease pathogenesis resulting from an inability to access primary AEC2s from affected children. Here, we report the generation of AEC2s from affected patient induced pluripotent stem cells (iPSCs) carrying homozygous versions of multiple ABCA3 mutations. We generated syngeneic CRISPR/Cas9 gene-corrected and uncorrected iPSCs and ABCA3-mutant knockin ABCA3:GFP fusion reporter lines for in vitro disease modeling. We observed an expected decreased capacity for surfactant secretion in ABCA3-mutant iPSC-derived AEC2s (iAEC2s), but we also found an unexpected epithelial-intrinsic aberrant phenotype in mutant iAEC2s, presenting as diminished progenitor potential, increased NFκB signaling, and the production of pro-inflammatory cytokines. The ABCA3:GFP fusion reporter permitted mutant-specific, quantifiable characterization of lamellar body size and ABCA3 protein trafficking, functional features that are perturbed depending on ABCA3 mutation type. Our disease model provides a platform for understanding ABCA3 mutation-mediated mechanisms of alveolar epithelial cell dysfunction that may trigger chILD pathogenesis.
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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.