New Anti-Fibrotic Strategies for Keloids: Insights From Single-Cell Multi-Omics

Area of Science:

• Dermatology
• Molecular Biology
• Cell Biology

Background:

• Keloids are challenging pathological scars with high recurrence rates.
• Current keloid treatments have inconsistent outcomes.
• Understanding keloid pathogenesis requires exploring cellular heterogeneity.

Purpose of the Study:

• To investigate the cellular heterogeneity and molecular mechanisms of keloids.
• To identify key fibroblast subpopulations involved in keloid formation.
• To explore potential therapeutic targets for keloid treatment.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of keloid and normal skin samples.
• Enrichment analysis and cell-cell communication analysis.
• Trajectory analysis, spatial transcriptomics, and flow cytometry.

Main Results:

• Identified distinct fibroblast subpopulations in keloids, including prevalent POSTN+ mesenchymal fibroblasts with high TGF-β signaling.
• Found IGFBP2+ fibroblasts abundant in normal skin with anti-fibrotic potential.
• Discovered an endothelial cell subpopulation (EC10) with mesenchymal activation characteristics contributing to abnormal angiogenesis.

Conclusions:

• POSTN+ fibroblasts promote keloid fibrosis, while IGFBP2+ fibroblasts possess anti-fibrotic properties.
• Specific endothelial cells and fibroblasts interact to drive pathological processes in keloids.
• IGFBP2+ fibroblasts represent a promising therapeutic target for novel anti-fibrotic strategies.