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Related Experiment Video

Updated: Sep 20, 2025

A Multi-Cue Bioreactor to Evaluate the Inflammatory and Regenerative Capacity of Biomaterials under Flow and Stretch

A Multi-Cue Bioreactor to Evaluate the Inflammatory and Regenerative Capacity of Biomaterials under Flow and Stretch

Published on: December 10, 2020

Spatial multiomics decipher fibroblast-macrophage dynamics in systemic sclerosis.

Zhijian Li¹, Aleix Rius Rigau², Wenjie Xie³

¹Broad Institute of MIT and Harvard, Cambridge, MA, USA; Molecular Pathology Unit, Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.

Annals of the Rheumatic Diseases

|May 23, 2025

Summary

Systemic sclerosis (SSc) involves fibroblast and macrophage interactions in fibrotic niches. Targeting CXCR4 shows potential to reduce fibrosis in SSc, offering new therapeutic avenues.

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Area of Science:

Connective tissue diseases
Immunology
Genomics

Background:

Stromal-immune cell interactions are crucial in systemic sclerosis (SSc) pathogenesis.
The spatial organization and communication networks driving fibrogenesis in SSc remain incompletely understood.

Purpose of the Study:

To investigate tissue organization and cell coordination in SSc skin.
To gain spatiotemporal insights into SSc disease mechanisms.
To bridge the gap between omics data and precision medicine for SSc.

Main Methods:

Spatial transcriptomics (10× Visium and Stereo-seq) on SSc and control skin biopsies.
Spatial proteomics and single-cell RNA sequencing.
In vivo and in vitro validation studies in SSc models.

Main Results:

Identified expanded fibrotic niches enriched with fibroblasts and macrophages in SSc, correlating with disease severity.
Characterized disease-specific fibroblast and macrophage states and their spatial interactions.
Discovered ACKR3's role in regulating macrophage recruitment and demonstrated that CXCR4 inhibition reduces fibrosis in experimental models.

Conclusions:

A spatially resolved atlas reveals dynamic fibroblast-macrophage interplay driving fibrotic niche expansion in SSc.
These findings provide spatiotemporal insights into SSc pathogenesis.
The study lays the groundwork for advanced mechanistic and therapeutic strategies in SSc.