Systemic sclerosis & Raynaud's

RUNX1 is expressed in a subpopulation of dermal fibroblasts and is associated with disease severity of systemic sclerosis

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

RUNX1 is associated with more severe SSc fibrosis and is associated with a subpopulation of dermal fibroblasts implicated in fibrosis.

Study context

Population
Systemic sclerosis (SSc) skin and dermal fibroblasts from multiple cohorts
Methodological detailsgene expression, genome-wide DNA methylation and single-cell RNA-seq analyses, siRNA, pharmacologic inhibition and CRISPR knockout in 2-dimensional and 3-dimensional fibroblast cultures
  • Gene expression, genome-wide DNA methylation and single-cell RNA-seq analyses
  • siRNA, pharmacologic inhibition and CRISPR knockout in 2-dimensional and 3-dimensional fibroblast cultures

Main finding

As reported in the abstract

  • Severity of dermal fibrosis associated with RUNX1 expression levels in SSc skin (multiple cohorts)
  • Hypomethylated CpG sites proximal to the RUNX1 gene, implicating a potential role in increased RUNX1 expression
  • RUNX1 higher in fibroblast subpopulations enriched in SSc, believed to contribute to fibrosis (single-cell RNA-seq)
  • RUNX1 CRISPR knockout reduced alpha smooth muscle actin expression
  • RUNX1 inhibition reduced fibroblast activation, contraction, extracellular matrix components and proliferation rates, including SFRP4, LUM and COL1A1

Original publication

RUNX1 is expressed in a subpopulation of dermal fibroblasts and is associated with disease severity of systemic sclerosis. Ann Rheum Dis. Published 11 December 2025. doi:10.1016/j.ard.2025.10.033

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