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Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting
Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604336/ https://www.ncbi.nlm.nih.gov/pubmed/36293401 http://dx.doi.org/10.3390/ijms232012549 |
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author | Yeo, Natalie Jia Ying Wazny, Vanessa Nguyen, Nhi Le Uyen Ng, Chun-Yi Wu, Kan Xing Fan, Qiao Cheung, Chui Ming Gemmy Cheung, Christine |
author_facet | Yeo, Natalie Jia Ying Wazny, Vanessa Nguyen, Nhi Le Uyen Ng, Chun-Yi Wu, Kan Xing Fan, Qiao Cheung, Chui Ming Gemmy Cheung, Christine |
author_sort | Yeo, Natalie Jia Ying |
collection | PubMed |
description | Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research. |
format | Online Article Text |
id | pubmed-9604336 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96043362022-10-27 Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting Yeo, Natalie Jia Ying Wazny, Vanessa Nguyen, Nhi Le Uyen Ng, Chun-Yi Wu, Kan Xing Fan, Qiao Cheung, Chui Ming Gemmy Cheung, Christine Int J Mol Sci Article Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research. MDPI 2022-10-19 /pmc/articles/PMC9604336/ /pubmed/36293401 http://dx.doi.org/10.3390/ijms232012549 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/). |
spellingShingle | Article Yeo, Natalie Jia Ying Wazny, Vanessa Nguyen, Nhi Le Uyen Ng, Chun-Yi Wu, Kan Xing Fan, Qiao Cheung, Chui Ming Gemmy Cheung, Christine Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting |
title | Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting |
title_full | Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting |
title_fullStr | Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting |
title_full_unstemmed | Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting |
title_short | Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting |
title_sort | single-cell transcriptome of wet amd patient-derived endothelial cells in angiogenic sprouting |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604336/ https://www.ncbi.nlm.nih.gov/pubmed/36293401 http://dx.doi.org/10.3390/ijms232012549 |
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