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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...

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Autores principales: Yeo, Natalie Jia Ying, Wazny, Vanessa, Nguyen, Nhi Le Uyen, Ng, Chun-Yi, Wu, Kan Xing, Fan, Qiao, Cheung, Chui Ming Gemmy, Cheung, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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