ArticleJCI insight2019
Single cell RNA sequencing identifies TGFβ as a key regenerative cue following LPS-induced lung injury.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed.
- Early cell-autonomous and niche-mediated epithelial response to influenza infection in primary alveolar organoids.JCI insight · 2026Article
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- A precision approach to translational research in acute lung injury.American journal of respiratory and critical care medicine · 2026Article
- Concurrent jamming and mesenchymal-to-epithelial transitions during airway basal stem cell differentiation.iScience · 2026Article
- Leveraging factors that control alveolar epithelial cell fate enables large-scale expansion for lung tissue engineering.The Journal of clinical investigation · 2026Article
- Identification of stem cell marker-positive subpopulations in the vocal fold of the larynx through transcriptomic analyses.Nature communications · 2026Article
- Alveolar-Basal Intermediates Drive Pulmonary Fibrosis via Coordination of a Pro-Fibrotic Signaling Niche in Silicosis.bioRxiv : the preprint server for biology · 2026Article
- The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells.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
- Airway Goblet Metaplasia Resulting from YAP/TAZ Deletion Drives Pulmonary Inflammatory Responses.American journal of respiratory cell and molecular biology · 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
- Modulation of an aberrant basal cell program in human alveolar epithelial spheroids and lung slices.Respiratory research · 2025Article
- Review
- Regulation of inflammatory lung injury and repair by transforming growth factors.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Early cell autonomous and niche-mediated alveolar epithelial response to influenza infection in primary lung organoids.bioRxiv : the preprint server for biology · 2025Article
- Stress, plasticity, and fibrosis: unfolding the role of the IRE1α/RIDD/Fgfr2 axis.The Journal of clinical investigation · 2025Article
- Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice.The Journal of clinical investigation · 2025Article
- A molecular circuit regulates fate plasticity in emerging and adult AT2 cells.Nature communications · 2025Article
- Aberrant intermediate alveolar epithelial cells promote pathogenic activation of lung fibroblasts in preclinical fibrosis models.Nature communications · 2025Article
- Staged Construction of Pluripotent Stem Cell Lung Models for Assessing Respiratory Toxicity of Environmental Pollutants.Environment & health (Washington, D.C.) · 2025Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Many lung diseases result from a failure of efficient regeneration of damaged alveolar epithelial cells (AECs) after lung injury. During regeneration, AEC2s proliferate to replace lost cells, after which proliferation halts and some AEC2s transdifferentiate into AEC1s to restore normal alveolar structure and function. Although the mechanisms underlying AEC2 proliferation have been studied, the mechanisms responsible for halting proliferation and inducing transdifferentiation are poorly understood. To identify candidate signaling pathways responsible for halting proliferation and inducing transdifferentiation, we performed single cell RNA sequencing on AEC2s during regeneration in a murine model of lung injury induced by intratracheal LPS. Unsupervised clustering revealed distinct subpopulations of regenerating AEC2s: proliferating, cell cycle arrest, and transdifferentiating. Gene expression analysis of these transitional subpopulations revealed that TGFβ signaling was highly upregulated in the cell cycle arrest subpopulation and relatively downregulated in transdifferentiating cells. In cultured AEC2s, TGFβ was necessary for cell cycle arrest but impeded transdifferentiation. We conclude that during regeneration after LPS-induced lung injury, TGFβ is a critical signal halting AEC2 proliferation but must be inactivated to allow transdifferentiation. This study provides insight into the molecular mechanisms regulating alveolar regeneration and the pathogenesis of diseases resulting from a failure of regeneration.
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