Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/168553
Title: Single-cell transcriptome of wet AMD patient-derived endothelial cells in angiogenic sprouting
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
Keywords: Science::Medicine
Issue Date: 2022
Source: 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
Project: MOE2018-T2-1-042 
RG88/21 
SPF2014/002 
Journal: International Journal of Molecular Sciences 
Abstract: 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.
URI: https://hdl.handle.net/10356/168553
ISSN: 1661-6596
DOI: 10.3390/ijms232012549
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Institute of Molecular and Cell Biology, A*STAR 
Rights: © 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/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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