Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/168553
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dc.contributor.authorYeo, Natalie Jia Yingen_US
dc.contributor.authorWazny, Vanessaen_US
dc.contributor.authorNhi Le Uyen Nguyenen_US
dc.contributor.authorNg, Chun Yien_US
dc.contributor.authorWu, Kan Xingen_US
dc.contributor.authorFan, Qiaoen_US
dc.contributor.authorCheung, Gemmy Chui Mingen_US
dc.contributor.authorCheung, Christineen_US
dc.date.accessioned2023-06-05T07:44:18Z-
dc.date.available2023-06-05T07:44:18Z-
dc.date.issued2022-
dc.identifier.citationYeo, 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/ijms232012549en_US
dc.identifier.issn1661-6596en_US
dc.identifier.urihttps://hdl.handle.net/10356/168553-
dc.description.abstractAge-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.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.language.isoenen_US
dc.relationMOE2018-T2-1-042en_US
dc.relationRG88/21en_US
dc.relationSPF2014/002en_US
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.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/).en_US
dc.subjectScience::Medicineen_US
dc.titleSingle-cell transcriptome of wet AMD patient-derived endothelial cells in angiogenic sproutingen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.organizationInstitute of Molecular and Cell Biology, A*STARen_US
dc.identifier.doi10.3390/ijms232012549-
dc.description.versionPublished versionen_US
dc.identifier.pmid36293401-
dc.identifier.scopus2-s2.0-85140816612-
dc.identifier.issue20en_US
dc.identifier.volume23en_US
dc.identifier.spage12549en_US
dc.subject.keywordsAge-Related Macular Degenerationen_US
dc.subject.keywordsBlood Outgrowth Endothelial Cellsen_US
dc.description.acknowledgementThe 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.en_US
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