Systemic sclerosis & Raynaud's
Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease
Authors' conclusion
These 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 SPP1hi macrophages.
Study context
- Population
- Explanted SSc-ILD and control human lungs
- Comparison
- Explanted SSc-ILD lungs vs control lungs
- Outcome
- Chromatin accessibility dynamics and transcription factors driving profibrotic gene programmes in fibroblasts and macrophages
Methodological detailsmultiomic single-nucleus assay for transposase-accessible (ATAC)/RNA-sequencing, ChromBPNet neural network analysis, HALO hierarchical causal modelling
- Multiomic single-nucleus ATAC/RNA-sequencing
- ChromBPNet neural network analysis
- HALO hierarchical causal modelling
Main finding
As reported in the abstract
- ChromBPNet inferred increased transcription factor binding to profibrotic genes, incl. CTHRC1 and ADAM12 in fibroblasts and SPP1 and CCL18 in macrophages
- SSc-ILD fibroblasts: increased binding and enhancer activity by AP-1, RUNX and EGR transcription factors to profibrotic genes
- Macrophages: enhanced binding and activity of AP-1 and bHLH-ZIP transcription factors in genes regulating the SPP1hi phenotype
- HALO confirmed AP-1, RUNX and EGR activity controlling profibrotic gene programmes
Original publication
Altered AP-1, RUNX, and EGR chromatin dynamics drive human fibrotic lung disease. Ann Rheum Dis. Published 31 December 2025. doi:10.
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