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 reti...

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Main Authors: Yeo, Natalie Jia Ying, Wazny, Vanessa, Nhi Le Uyen Nguyen, Ng, Chun Yi, Wu, Kan Xing, Fan, Qiao, Cheung, Gemmy Chui Ming, Cheung, Christine
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/168553
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1685532023-06-11T15:41:07Z Single-cell transcriptome of wet AMD patient-derived endothelial cells in angiogenic sprouting Yeo, Natalie Jia Ying Wazny, Vanessa Nhi Le Uyen Nguyen Ng, Chun Yi Wu, Kan Xing Fan, Qiao Cheung, Gemmy Chui Ming Cheung, Christine Lee Kong Chian School of Medicine (LKCMedicine) Institute of Molecular and Cell Biology, A*STAR Science::Medicine Age-Related Macular Degeneration Blood Outgrowth Endothelial Cells 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. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Published version The team from Nanyang Technological University Singapore was funded by the Nanyang Assistant Professorship and Academic Research Fund grants (MOE2018-T2-1-042 and RG88/21) from the Ministry of Education, Singapore. N.J.Y.Y and V.W. were supported by the Nanyang President’s Graduate Scholarship. C.C. and C.M.G.C. were funded by the SERI-IMCB Program in Retinal Angiogenic Diseases (SIPRAD) grant (SPF2014/002) from Agency for Science, Technology and Research, Singapore. 2023-06-05T07:44:18Z 2023-06-05T07:44:18Z 2022 Journal Article Yeo, N. J. Y., Wazny, V., Nhi Le Uyen Nguyen, Ng, C. Y., Wu, K. X., Fan, Q., Cheung, G. C. M. & Cheung, C. (2022). Single-cell transcriptome of wet AMD patient-derived endothelial cells in angiogenic sprouting. International Journal of Molecular Sciences, 23(20), 12549-. https://dx.doi.org/10.3390/ijms232012549 1661-6596 https://hdl.handle.net/10356/168553 10.3390/ijms232012549 36293401 2-s2.0-85140816612 20 23 12549 en MOE2018-T2-1-042 RG88/21 SPF2014/002 International Journal of Molecular Sciences © 2022 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/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Age-Related Macular Degeneration
Blood Outgrowth Endothelial Cells
spellingShingle Science::Medicine
Age-Related Macular Degeneration
Blood Outgrowth Endothelial Cells
Yeo, Natalie Jia Ying
Wazny, Vanessa
Nhi Le Uyen Nguyen
Ng, Chun Yi
Wu, Kan Xing
Fan, Qiao
Cheung, Gemmy Chui Ming
Cheung, Christine
Single-cell transcriptome of wet AMD patient-derived endothelial cells in angiogenic sprouting
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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Yeo, Natalie Jia Ying
Wazny, Vanessa
Nhi Le Uyen Nguyen
Ng, Chun Yi
Wu, Kan Xing
Fan, Qiao
Cheung, Gemmy Chui Ming
Cheung, Christine
format Article
author Yeo, Natalie Jia Ying
Wazny, Vanessa
Nhi Le Uyen Nguyen
Ng, Chun Yi
Wu, Kan Xing
Fan, Qiao
Cheung, Gemmy Chui Ming
Cheung, Christine
author_sort Yeo, Natalie Jia Ying
title 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_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_sort single-cell transcriptome of wet amd patient-derived endothelial cells in angiogenic sprouting
publishDate 2023
url https://hdl.handle.net/10356/168553
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