ArticleThe American journal of pathology2022
Fatal COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome Is Associated with Incomplete Alveolar Type 1 Epithelial Cell Differentiation from the Transitional State without Fibrosis.
Article in The American journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 0 citations in OpenAlex.
- Meta-Analysis of COVID-19 BAL Single-Cell RNA Sequencing Reveals Alveolar Epithelial Transitions and Unique Alveolar Epithelial Cell Fates.American journal of respiratory cell and molecular biology · 2023Pooled it
- SARS-CoV-2 infection produces an IL-33-dependent chronic eosinophilic pneumonia and muco-inflammatory airways disease in Scnn1b-Tg mice.JCI insight · 2026Article
- Alveolar Epithelial Cell Loss of the Mitochondrial Regulator TFAM Drives Progressive Lung Fibrosis.bioRxiv : the preprint server for biology · 2026Article
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- A precision approach to translational research in acute lung injury.American journal of respiratory and critical care medicine · 2026Article
- Alveolar-Basal Intermediates Drive Pulmonary Fibrosis via Coordination of a Pro-Fibrotic Signaling Niche in Silicosis.bioRxiv : the preprint server for biology · 2026Article
- Multi-Omic and Single-Cell Approaches for Elucidating Cell Biology and Pathobiology of Lung Disease.American journal of respiratory cell and molecular biology · 2026Review
- Transcriptomic signature-guided depletion of intermediate alveolar epithelial cells ameliorates pulmonary fibrosis in mice.Nature communications · 2026Article
- Beyond immunomodulation: mechanisms and synergistic strategies of mesenchymal stem cells in promoting alveolar epithelial and endothelial repair in ARDS.Frontiers in immunology · 2026Review
- Isogenic induced-pluripotent-stem-cell-derived airway- and alveolus-on-chip models reveal specific innate immune responses.Nature biomedical engineering · 2025Article
- Autoimmune reactions to ACE2 triggered by SARS-CoV-2 S protein and their histopathological consequences.Scientific reports · 2025Article
- Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice.The Journal of clinical investigation · 2025Article
- Single-dose cathepsin L CRISPR nanotherapy mitigates PASC-like lung damage in hamsters.Nano research · 2025Article
- Genetic and Inflammatory Signatures Associated With Worse Prognosis in Hospitalized Patients With Severe SARS-CoV-2 Infection With and Without Diabetes.Journal of medical virology · 2025Article
- Longitudinal importance of the soluble receptor for advanced glycation end-products in nonintubated hospitalized patients with COVID-19 pneumonia.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Postinfectious Pulmonary Complications: Establishing Research Priorities to Advance the Field: An Official American Thoracic Society Workshop Report.Annals of the American Thoracic Society · 2024Review
- Stem cells, cell therapies, and bioengineering in lung biology and diseases 2023.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Pumping Iron Burns Fat in Lung Injury.American journal of respiratory cell and molecular biology · 2024Article
- Geroscience and pathology: a new frontier in understanding age-related diseases.Pathology oncology research : POR · 2024Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; recovery requires epithelial regeneration. During physiological regeneration in mice, type 2 AECs (AEC2s) proliferate, exit the cell cycle, transiently assume a transitional state, then differentiate into type 1 AECs (AEC1s); in humans, persistence of the transitional state is associated with pulmonary fibrosis. It is unknown whether transitional cells emerge and differentiate into AEC1s without fibrosis in human ARDS and why transitional cells differentiate into AEC1s during physiological regeneration but persist in fibrosis. We hypothesized that incomplete but ongoing AEC1 differentiation from transitional cells without fibrosis may underlie persistent barrier permeability and acute respiratory failure in ARDS. Immunostaining of postmortem ARDS lungs revealed abundant transitional cells without fibrosis. They were typically cuboidal or partially spread, sometimes flat, and occasionally expressed AEC1 markers. Immunostaining and/or single-cell RNA sequencing revealed that transitional cells in mouse models of physiological regeneration, ARDS, and fibrosis express markers of cell cycle exit but only in fibrosis express a specific senescence marker. Thus, in severe, fatal early ARDS, AEC1 differentiation from transitional cells is incomplete, underlying persistent barrier permeability and respiratory failure but ongoing without fibrosis; senescence of transitional cells may be associated with pulmonary fibrosis.
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Registered trials
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