ArticleAmerican journal of human genetics2023
The COPD GWAS gene ADGRG6 instructs function and injury response in human iPSC-derived type II alveolar epithelial cells.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- Macrophages orchestrate antiviral defense and epithelial repair in a human iPSC-derived alveolar air-liquid interface.JCI insight · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- AT2-intrinsic Z-AAT expression drives conserved inflammatory and proteotoxic stress responses and predisposes to emphysema.bioRxiv : the preprint server for biology · 2026Article
- New approaches to uncover COPD pathobiology and develop therapies.JCI insight · 2026Review
- Cross-Trait Genome-Wide Association Study Identifies Shared Genetic Architecture Between COPD and Retinal Vascular Phenotypes.International journal of chronic obstructive pulmonary disease · 2026Article
- Domain-specific N-glycosylation of the adhesion G-protein-coupled receptor ADGRG6 N-terminal fragment regulates trafficking, proteolytic processing, and signaling.Molecular biology of the cell · 2025Article
- Recent Advancements in the Generation and Application of Therapeutic Cell Populations for Lung Epithelial Repair.Journal of tissue engineering and regenerative medicine · 2025Review
- 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
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Emphysema and chronic obstructive pulmonary disease (COPD) most commonly result from the effects of environmental exposures in genetically susceptible individuals. Genome-wide association studies have implicated ADGRG6 in COPD and reduced lung function, and a limited number of studies have examined the role of ADGRG6 in cells representative of the airway. However, the ADGRG6 locus is also associated with DLCO/VA, an indicator of gas exchange efficiency and alveolar function. Here, we sought to evaluate the mechanistic contributions of ADGRG6 to homeostatic function and disease in type 2 alveolar epithelial cells. We applied an inducible CRISPR interference (CRISPRi) human induced pluripotent stem cell (iPSC) platform to explore ADGRG6 function in iPSC-derived AT2s (iAT2s). We demonstrate that ADGRG6 exerts pleiotropic effects on iAT2s including regulation of focal adhesions, cytoskeleton, tight junctions, and proliferation. Moreover, we find that ADGRG6 knockdown in cigarette smoke-exposed iAT2s alters cellular responses to injury, downregulating apical complexes in favor of proliferation. Our work functionally characterizes the COPD GWAS gene ADGRG6 in human alveolar epithelium.
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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.