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Spatial analyses of early, untreated SSc skin identify a proinflammatory vascular niche of macrophage-fibroblast signaling

GSE312932 Homo sapiens (human) Other 10 samples Submitted 2025/12/12 Platform GPL33762
At a glance

human · 10 samples

Organism
Homo sapiens (human)
Samples
10 samples
Data you can get
A processed table (series matrix) and supplementary files from NCBI.
Summary (written by the submitters)
Uncovering the early interactions and spatial distribution of dermal fibroblasts and immune cells in treatment-naïve diffuse cutaneous systemic sclerosis (dcSSc) patients is critical to understanding the initiating events skin fibrosis. We generated an integrated multiomic dataset of early, treatment naïve dcSSc skin. Skin biopsies were analyzed by single-nuclei multiome sequencing (snRNA-seq and snATAC-seq) and two different paired spatial transcriptomic platforms to comprehensively describe the molecular changes in these individuals.
Read the full summary ↓
We identified a proinflammatory niche within papillary, hypodermis, and vascular niches, that are enriched for activated myeloid cells and proinflammatory fibroblasts characterized by expression of proinflammatory cytokines. Pathway analyses showed significant enrichment of PI3K-AKT-mTOR signaling pathway expression in these cellular niches, driven by profibrotic growth factor signaling networks. Macrophage subclustering showed SSc-specific macrophage activation of IL6-JAK-STAT signaling and the enrichment of oxidative phosphorylation pathways. Ligand-receptor analysis revealed that SSc macrophages secrete PDGF and TGFB to activate the inflammatory SSc-dominant fibroblast subclusters. Spatial transcriptomic analyses showed infiltrating macrophages secreted PDGF and TGFB, modulating fibroblast activation in these niches. Multiomic data integration and spatial transcriptomic neighborhood analysis showed co-localization of fibroblasts, macrophages, and T cells around the vasculature. These data suggest that interactions between activated immune cells and proinflammatory fibroblasts around vascular niches are an early event in scleroderma pathogenesis.
This dataset
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Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

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Supplementary files

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All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE312932_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Also filed as BioProject PRJNA1377624. Searching any of these in the dataset finder brings you back here.

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