Systemic sclerosis & Raynaud's
Spatial multiomics decipher fibroblast–macrophage dynamics in systemic sclerosis
Authors' conclusion
Our spatially resolved atlas uncovered dynamic fibroblast-macrophage interplay as a hallmark of fibrotic niche expansion.
Study context
- Population
- Skin biopsies from patients with diffuse cutaneous systemic sclerosis (SSc) and healthy controls14 skin biopsies analysed
- Participants
- 14 participants
- Comparison
- Diffuse cutaneous SSc vs healthy controls
- Diffuse cutaneous SScn = 10
- Healthy controlsn = 4reference
- Outcome
- Tissue organisation and cell coordination in SSc skin
Methodological detailsspatial transcriptomics (10× Visium), Stereo-seq, spatial proteomics and single-cell RNA sequencing confirmation, SSc mouse models and wound-healing reindeer models, in vivo and in vitro validation
- Spatial transcriptomics (10× Visium)
- Stereo-seq, spatial proteomics and single-cell RNA sequencing confirmation
- SSc mouse models and wound-healing reindeer models
- In vivo and in vitro validation
Main finding
As reported in the abstract
- Significant expansion of fibrotic niches enriched with fibroblasts and macrophages in SSc, correlating with clinical severity
- Disease-specific cell states of fibroblasts and macrophages identified, with spatial dependency and cell-cell communication evaluated
- Stratification based on signature genes identified patients with SSc with progressive disease and treatment-nonresponsive phenotype
- ACKR3 (CXCL12 decoy receptor) selectively expressed in myofibroblast progenitors, diminishing during differentiation towards mature myofibroblast; potentially regulating CXCL12/CXCR4-mediated proinflammatory macrophage recruitment
- CXCR4 inhibition attenuated skin and lung fibrosis in experimental fibrosis mouse models
Original publication
Spatial multiomics decipher fibroblast–macrophage dynamics in systemic sclerosis. Ann Rheum Dis. Published 22 May 2025. doi:10.
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