***-cell transcriptomics identifies cell-specific signatures of pathological angiogenesis

作     者：Gael Cagnone Sheetal Pundir Nick Kim Emilie Heckel Jin Sung Kim Perrine Gaub Florian Wunnemann Piet van Vliet Severine Leclerc Gregor Andelfinger Sylvain Chemtob Jean-Sebastien Joyal 

作者机构：CHU Ste-Justine Research CenterUniversitéde MontréalMontréalQCCanada Faculty of MedicineDepartment of Pharmacology and PhysiologyUniversitéde MontréalMontréalQCCanada Faculty of MedicineDepartment of PediatricsUniversity of MontrealUniversitéde MontréalMontréalQCCanada Department of Pharmacology and TherapeuticsMcGill UniversityMontréalQCCanada 

出 版 物：《Annals of Eye Science》 (眼科学年鉴（英文）)

年 卷 期：2019年第1期

页      面：215-215页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Single-cell RNAseq angiogenesis pathological vascularization metabolism inflammation 

摘      要：Background:To treat vascular proliferative diseases,anti-VEGF therapies have shown systemic adverse effects attributable to the lack of selectivity between pathological and physiological ***,identifying the molecular mechanisms that are only specific to pathological cell types is crucial to develop better precision ***:Here,we used different cell type enrichment approaches combined with single-cell RNA sequencing to define the transcriptomic changes within each retinal cell types in a mouse model of ischemic *** retinal model develops pathological neovascularization(NV)in response to local hypoxia following oxygen-induced vessel obliteration(P7 to P12).The NV phenotype is characterized by the progressive appearance of vascular tufts resulting from misguided,abnormal proliferation of endothelial cells that we monitored at 3 consecutive time points-P12,P14 and P17(peak of NV).Results:By following the dynamic response to hypoxia,our experimental design reveals how pathological angiogenesis is specifically associated with significant metabolic adaptations in different subtypes of endothelial cells(i.e.,Tips vs Stalk cells).We also identify a pathological subtype of glial cells over-expressing VEGFA and pro-inflammatory IL-1 receptor *** subtype of activated glial cells was targeted using selective IL1R antagonist treatment which reduced glial activation,inflammation,NV and promotes physiological angiogenesis,therefore improving tissue ***:Our results illustrate how analyzing cell type heterogeneity in tissues developing pathological angiogenesis allows establishing better targeting therapies to restore vascular integrity.