ArticleCell reports2019
Dlk1-Mediated Temporal Regulation of Notch Signaling Is Required for Differentiation of Alveolar Type II to Type I Cells during Repair.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 129 citations in OpenAlex.
- Novel netrin-1-Unc5b-Klf4 axis balances AT2 survival in experimental bronchopulmonary dysplasia.American journal of respiratory cell and molecular biology · 2026Article
- Targeting alveolar type II cell dysfunction in idiopathic pulmonary fibrosis: Molecular mechanisms and emerging therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.Microorganisms · 2026Review
- Clustering Single-Cell RNA-Seq Data with Low-Rank Matrix Factorization and Local Graph Regularization.Interdisciplinary sciences, computational life sciences · 2026Article
- Review
- Unlocking Alveolar Regeneration: AT2 Stem Cells, Signaling Networks, and Therapeutic Frontiers.Stem cell reviews and reports · 2026Review
- Advances in understanding mitophagy's role in lung injury.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Bmp9 regulates Notch signaling and the temporal dynamics of angiogenesis via Lunatic Fringe.Developmental cell · 2026Article
- TP53/TAU axis regulates microtubule bundling to control alveolar stem cell-mediated regeneration.The Journal of clinical investigation · 2026Article
- Age-dependent immune responses and resident cell dynamics in young mice following pneumonia.iScience · 2026Article
- Transcriptomic signature-guided depletion of intermediate alveolar epithelial cells ameliorates pulmonary fibrosis in mice.Nature communications · 2026Article
- Single-cell lineage tracing in tumor organoids identifies expansion states depicting the origin and progression of lung adenocarcinoma.Frontiers in immunology · 2026Article
- Large-scale proteome profiling identifies circulating biomarkers for disease activity and organ involvement in ANCA-associated vasculitides.Frontiers in immunology · 2026Article
- Cellular plasticity and regenerative mechanisms in the lung.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Modulation of an aberrant basal cell program in human alveolar epithelial spheroids and lung slices.Respiratory research · 2025Article
- Postnatal sustentacular cells as chromaffin progenitors and tumor cells of origin in VHL-related paragangliomas.NPJ precision oncology · 2025Article
- A molecular circuit regulates fate plasticity in emerging and adult AT2 cells.Nature communications · 2025Article
- Evidence that metformin promotes fibrosis resolutionActa pharmaceutica Sinica. B · 2025Article
- Staged Construction of Pluripotent Stem Cell Lung Models for Assessing Respiratory Toxicity of Environmental Pollutants.Environment & health (Washington, D.C.) · 2025Review
- Building blocks for lung regeneration: Stem cells and niches.Molecules and cells · 2025Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Lung alveolar type I cells (AT1) and alveolar type II cells (AT2) regulate the structural integrity and function of alveoli. AT1, covering ∼95% of the surface area, are responsible for gas exchange, whereas AT2 serve multiple functions, including alveolar repair through proliferation and differentiation into AT1. However, the signaling mechanisms for alveolar repair remain unclear. Here, we demonstrate, in Pseudomonas aeruginosa-induced acute lung injury in mice, that non-canonical Notch ligand Dlk1 (delta-like 1 homolog) is essential for AT2-to-AT1 differentiation. Notch signaling was activated in AT2 at the onset of repair but later suppressed by Dlk1. Deletion of Dlk1 in AT2 induced persistent Notch activation, resulting in stalled transition to AT1 and accumulation of an intermediate cell population that expressed low levels of both AT1 and AT2 markers. Thus, Dlk1 expression leads to precisely timed inhibition of Notch signaling and activates AT2-to-AT1 differentiation, leading to alveolar repair.
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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.