ArticleCell stem cell2025
Hypoxia promotes airway differentiation in the human lung epithelium.
Article in Cell stem cell, 2025. 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.
- Niche-Mediated Neural Priming Enables Robust and Scalable Generation of Human Choroid Plexus Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Robust generation of distal respiratory airway organoids by an engineered cuboid chip.Journal of nanobiotechnology · 2026Article
- Hypoxia inducible factors regulate pneumovirus replication by enhancing innate immune sensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mapping SET1B chromatin interactions with DamID using DamMapper, a comprehensive Snakemake workflow.BMC genomics · 2025Article
- Single cell transcriptional analysis of human adenoids identifies molecular features of airway microfold cells.Mucosal immunology · 2025Article
- A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.The EMBO journal · 2025Article
- Human iPSC-Derived Blood Vessel Organoids for Studying Chronic Hypoxia-Induced Microvascular Dysfunction.The journal of histochemistry and cytochemistry : official journal of the Histochemistry SocietyArticle
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Human lungs experience dynamic oxygen tension during development. Here, we show that hypoxia directly regulates human lung epithelial cell identity using tissue-derived organoids. Fetal multipotent lung epithelial progenitors remain undifferentiated in a self-renewing culture condition under normoxia but spontaneously differentiate toward multiple airway cell types and inhibit alveolar differentiation under hypoxia. Using chemical and genetic tools, we demonstrate that hypoxia-induced airway differentiation depends on hypoxia-inducible factor (HIF) activity, with HIF1α and HIF2α differentially regulating progenitor fate decisions. KLF4 and KLF5 are direct HIF targets that promote basal and secretory cell fates. Moreover, hypoxia is sufficient to convert alveolar type 2 cells derived from both human fetal and adult lungs to airway cells, including aberrant basal-like cells that exist in human fibrotic lungs. These findings reveal roles for hypoxia and HIF activity in the developing human lung epithelium and have implications for aberrant cell fate changes in pathological lungs.
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Registered trials
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