Characterization of Vascular Niche in Systemic Sclerosis by Spatial Proteomics

Area of Science:

• Vascular biology
• Connective tissue diseases
• Immunology

Background:

• Systemic sclerosis (SSc) is a connective tissue disease offering insights into vascular pathology.
• Microvascular changes are early SSc indicators, but their underlying mechanisms remain unclear.
• Understanding SSc vasculopathy is crucial for addressing inflammation, autoimmunity, and fibrosis.

Purpose of the Study:

• To investigate vascular cell heterogeneity in SSc using spatial proteomics.
• To characterize cellular alterations within the vascular niches of SSc patients.
• To identify novel cell populations and their roles in SSc pathogenesis.

Main Methods:

• Spatial proteomic analysis of skin biopsies from SSc patients and controls.
• Imaging mass cytometry was employed to profile cellular composition.
• Single-cell level deconvolution of vascular and immune cells.

Main Results:

• Identified distinct subpopulations of blood vascular endothelial cells (VECs), lymphatic endothelial cells, and pericytes.
• Discovered a novel CD34+;αSMA+;CD31+ VEC population, increased in SSc and linked to endothelial-to-mesenchymal transition.
• Found this novel VEC population in proximity to immune cells and myofibroblasts, with counts correlating to fibrosis severity.

Conclusions:

• Spatial proteomics revealed significant vascular cell heterogeneity in SSc.
• The novel CD34+;αSMA+;CD31+ VEC population represents a key cellular player in SSc vasculopathy and fibrosis.
• These findings provide a cellular basis for understanding the interplay between vascular disease and fibrosis in SSc.