ArticleNature communications2025
Let-7 restrains an epigenetic circuit in AT2 cells to prevent fibrogenic intermediates in pulmonary fibrosis.
Article in Nature communications, 2025. 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.
- Lung-targeted hepatocyte growth factor mRNA restores alveolar structure in experimental emphysema.The European respiratory journal · 2026Article
- Loss of Function Dnmt3a Mutation Leads to Aberrant Neutrophil Migration.Experimental hematology · 2026Article
- The AGO2 adaptor LIMD1 expands the functional and evolutionary reach of microRNA targeting.Science advances · 2026Article
- The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.Microorganisms · 2026Review
- Transitional cell states at the crossroads of development, disease, and repair-regeneration.Physiological reviews · 2026Review
- Integrative single-cell and bulk transcriptomic analyses identifyJournal of thoracic disease · 2026Article
- Identification of Candidate mRNA and miRNA Molecules Associated with Tuberculosis Through Preliminary Analysis and Validation Using Clinical Samples.International journal of molecular sciences · 2026Article
- The chromatin remodeling complex PRC2 safeguards cell fate in alveolar epithelial type 2 cells.bioRxiv : the preprint server for biology · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- BACH1-mediated transcriptional repression of pro-angiogenic factors drives angiogenic impairment in hypertension.Frontiers in cardiovascular medicine · 2026Article
- Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.Frontiers in pharmacology · 2026Review
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions.Biomedicines · 2025Review
- A semi-supervised Bayesian approach for marker gene trajectory inference from single-cell RNA-seq data.Bioinformatics (Oxford, England) · 2025Article
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Advances in Expression Regulation, Molecular Targeting Mechanisms, and Therapeutic Applications of the Let-7 MicroRNA Family in Gastric Cancer.Oncology research · 2025Review
- The role of epigenetics in pulmonary fibrosis: recent advances in mechanistic insights and therapeutic implications.Frontiers in molecular biosciences · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses revealed that let-7afd loss disrupts histone acetylation and methylation, driving epigenetic reprogramming and altered gene transcription in profibrotic AT2 cells. This study identifies let-7 as a central hub linking unchecked oncogenic signaling to impaired AT2 cell plasticity and fibrogenesis.
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