Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin
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...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/13/1784 |
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| author | Marvin L. Frommer Benjamin J. Langridge Laura Awad Sara Jasionowska Christopher P. Denton David J. Abraham Jeries Abu-Hanna Peter E. M. Butler |
| author_facet | Marvin L. Frommer Benjamin J. Langridge Laura Awad Sara Jasionowska Christopher P. Denton David J. Abraham Jeries Abu-Hanna Peter E. M. Butler |
| author_sort | Marvin L. Frommer |
| collection | DOAJ |
| description | 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 <i>NTN1</i>, <i>VEGFD</i>, <i>MMP2</i>, <i>FGF2,</i> and <i>FNDC5</i>. 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. |
| first_indexed | 2024-03-11T01:45:14Z |
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| id | doaj.art-770c9e5305ea4aa4bbcbb43d3d848a1c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T01:45:14Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-770c9e5305ea4aa4bbcbb43d3d848a1c2023-11-18T16:20:00ZengMDPI AGCells2073-44092023-07-011213178410.3390/cells12131784Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma SkinMarvin L. Frommer0Benjamin J. Langridge1Laura Awad2Sara Jasionowska3Christopher P. Denton4David J. Abraham5Jeries Abu-Hanna6Peter E. M. Butler7Charles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UKCharles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UKCharles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UKCharles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UKCentre for Rheumatology, Department of Inflammation, Division of Medicine, University College London, London NW3 2QG, UKCentre for Rheumatology, Department of Inflammation, Division of Medicine, University College London, London NW3 2QG, UKCharles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UKCharles Wolfson Centre for Reconstructive Surgery, Royal Free Hospital, London NW3 2QG, UKAdipose-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 <i>NTN1</i>, <i>VEGFD</i>, <i>MMP2</i>, <i>FGF2,</i> and <i>FNDC5</i>. 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.https://www.mdpi.com/2073-4409/12/13/1784single-cell RNA sequencingsclerodermaskin fibrosisautologous fat graftingadipose-derived stem cellsADSC |
| spellingShingle | Marvin L. Frommer Benjamin J. Langridge Laura Awad Sara Jasionowska Christopher P. Denton David J. Abraham Jeries Abu-Hanna Peter E. M. Butler Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin Cells single-cell RNA sequencing scleroderma skin fibrosis autologous fat grafting adipose-derived stem cells ADSC |
| title | Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin |
| title_full | Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin |
| title_fullStr | Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin |
| title_full_unstemmed | Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin |
| title_short | Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin |
| title_sort | single cell analysis of adsc interactions with fibroblasts and endothelial cells in scleroderma skin |
| topic | single-cell RNA sequencing scleroderma skin fibrosis autologous fat grafting adipose-derived stem cells ADSC |
| url | https://www.mdpi.com/2073-4409/12/13/1784 |
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