ArticleAnnals of the rheumatic diseases2026
Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease.
Article in Annals of the rheumatic diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed.
- Macrophage heterogeneity in organ fibrosis in the era of single-cell omics.Molecular biology reports · 2026Review
- Non-Resolving Repair in Idiopathic Pulmonary Fibrosis: From Failed Cellular Transitions to Architectural Lock-In.International journal of molecular sciences · 2026Review
- The PPAR-gamma agonist pioglitazone alleviates bleomycin-induced lung fibrosis in male BALB/c mice.Multidisciplinary respiratory medicine · 2026Article
- Dynamic three-dimensional chromatin remodeling in lung disease: mechanistic principles, pathogenic regulatory networks, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Transcriptomic identification of IL-17/FOS-associated signaling in dartos fascia remodeling of pediatric concealed penis.Frontiers in pediatrics · 2026Article
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- HALO: hierarchical causal modeling for single cell multi-omics data.Nature communications · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
objectivesPulmonary fibrosis can result from autoimmune, inflammatory, or idiopathic conditions, including systemic sclerosis-associated interstitial lung disease (SSc-ILD). Previous studies have implicated myofibroblasts and SPP1
methodsTo determine the chromatin accessibility dynamics and transcription factors driving profibrotic gene programmes in human pulmonary fibrosis, we performed multiomic single-nucleus assay for transposase-accessible (ATAC)/RNA-sequencing on explanted SSc-ILD and control lungs. Using the neural network tool ChromBPNet, we analysed pseudobulk fibroblast and macrophage populations to infer transcription factor binding dynamics at single base-pair resolution. Hierarchical causal modelling for single-cell multiomics data (HALO), a novel algorithm developed to derive low-dimensional representations of sparse multiomics data, revealed transcription factor-regulatory element-gene networks.
resultsChromBPNet inferred increased transcription factor binding to profibrotic genes, including CTHRC1 and ADAM12 in fibroblasts, and SPP1 and CCL18 in macrophages. SSc-ILD fibroblasts showed increased binding and enhancer activity by AP-1, RUNX, and EGR transcription factors to profibrotic genes, whereas macrophages displayed enhanced binding and activity of AP-1 and basic helix-loop-helix (bHLH)-ZIP transcription factors in genes regulating the SPP1
conclusionsThese data provide comprehensive insights into the complexity of transcriptional control of SSc-ILD gene expression programmes and define specific AP-1, RUNX, and EGR enhancers in key myofibroblast marker genes CTHRC1 and ADAM12, and a bHLH-ZIP enhancer in SPP1
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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.