ArticleDevelopmental cell2023
Age-associated H3K9me2 loss alters the regenerative equilibrium between murine lung alveolar and bronchiolar progenitors.
Article in Developmental cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
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- Multi-Omic and Single-Cell Approaches for Elucidating Cell Biology and Pathobiology of Lung Disease.American journal of respiratory cell and molecular biology · 2026Review
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
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- Aging represses oncogenic KRAS-driven lung tumorigenesis and alters tumor suppression.Nature aging · 2025Article
- Epithelial damage and ageing: the perfect storm.Thorax · 2025Review
- Mechanisms and markers of lung ageing in health and disease.European respiratory review : an official journal of the European Respiratory Society · 2025Review
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- Progressive lung fibrosis: reprogramming a genetically vulnerable bronchoalveolar epithelium.The Journal of clinical investigation · 2025Review
- Alveolar epithelial type 2 cells in acute lung injury and acute respiratory distress syndrome: spatiotemporal fate and regulation.Burns & trauma · 2025Review
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- Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs.Toxicology reports · 2024Article
- ECM and epithelial stem cells: the scaffold of destiny.Frontiers in cell and developmental biology · 2024Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The lung contains multiple progenitor cell types, but how their responses are choreographed during injury repair and whether this changes with age is poorly understood. We report that histone H3 lysine 9 di-methylation (H3K9me2), mediated by the methyltransferase G9a, regulates the dynamics of distal lung epithelial progenitor cells and that this regulation deteriorates with age. In aged mouse lungs, H3K9me2 loss coincided with fewer alveolar type 2 (AT2) cell progenitors and reduced alveolar regeneration but increased the frequency and activity of multipotent bronchioalveolar stem cells (BASCs) and bronchiolar progenitor club cells. H3K9me2 depletion in young mice decreased AT2 progenitor activity and impaired alveolar injury repair. Conversely, H3K9me2 depletion increased chromatin accessibility of bronchiolar cell genes, increased BASC frequency, and accelerated bronchiolar cell injury repair. These findings indicate that during aging, the epigenetic regulation that coordinates lung progenitor cells' regenerative responses becomes dysregulated, aiding our understanding of age-related susceptibility to lung disease.
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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.