Frommer, Marvin L;
Langridge, Benjamin J;
Awad, Laura;
Jasionowska, Sara;
Denton, Christopher P;
Abraham, David J;
Abu-Hanna, Jeries;
(2023)
Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin.
Cells
, 12
(13)
, Article 1784. 10.3390/cells12131784.
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Abstract
Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand–receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour.
| Type: | Article |
|---|---|
| Title: | Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/cells12131784 |
| Publisher version: | https://doi.org/10.3390/cells12131784 |
| Language: | English |
| Additional information: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Single-cell RNA sequencing; scleroderma; skin fibrosis; autologous fat grafting; adipose-derived stem cells; ADSC; secretome; cellular therapies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173628 |
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