Taylor, XavierCisternas, PabloJury, NurMartinez, PabloHuang, XiaoqingYou, YanwenRedding-Ochoa, JavierVidal, RubenZhang, JieTroncoso, JuanLasagna-Reeves, Cristian A.2023-06-022023-06-022022-03-29Taylor X, Cisternas P, Jury N, et al. Activated endothelial cells induce a distinct type of astrocytic reactivity. Commun Biol. 2022;5(1):282. Published 2022 Mar 29. doi:10.1038/s42003-022-03237-8https://hdl.handle.net/1805/33429Reactive astrogliosis is a universal response of astrocytes to abnormal events and injuries. Studies have shown that proinflammatory microglia can polarize astrocytes (designated A1 astrocytes) toward a neurotoxic phenotype characterized by increased Complement Component 3 (C3) expression. It is still unclear if inflammatory stimuli from other cell types may also be capable of inducing a subset of C3+ neurotoxic astrocytes. Here, we show that a subtype of C3+ neurotoxic astrocytes is induced by activated endothelial cells that is distinct from astrocytes activated by microglia. Furthermore, we show that endothelial-induced astrocytes have upregulated expression of A1 astrocytic genes and exhibit a distinctive extracellular matrix remodeling profile. Finally, we demonstrate that endothelial-induced astrocytes are Decorin-positive and are associated with vascular amyloid deposits but not parenchymal amyloid plaques in mouse models and AD/CAA patients. These findings demonstrate the existence of potentially extensive and subtle functional diversity of C3+-reactive astrocytes.en-USAttribution 4.0 InternationalAstrocytesEndothelial cellsMicrogliaArticle