Cátia Gomes, Kang-Chieh Huang, Jade Harkin, Aaron Baker, Jason M Hughes, Yanling Pan, Kaylee Tutrow, Kirstin B VanderWall, Sailee S Lavekar, Melody Hernandez, Theodore R Cummins, Scott G Canfield, Jason S Meyer
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引用次数: 0
Abstract
Reactive astrocytes are known to exert detrimental effects upon neurons in several neurodegenerative diseases, yet our understanding of how astrocytes promote neurotoxicity remains incomplete, especially in human systems. In this study, we leveraged human pluripotent stem cell (hPSC) models to examine how reactivity alters astrocyte function and mediates neurodegeneration. hPSC-derived astrocytes were induced to a reactive phenotype, at which point they exhibited a hypertrophic profile and increased complement C3 expression. Functionally, reactive astrocytes displayed decreased intracellular calcium, elevated phagocytic capacity, and decreased contribution to the blood-brain barrier. Subsequently, co-culture of reactive astrocytes with a variety of neuronal cell types promoted morphological and functional alterations. Furthermore, when reactivity was induced in astrocytes from patient-specific hPSCs (glaucoma, Alzheimer's disease, and amyotrophic lateral sclerosis), the reactive state exacerbated astrocytic disease-associated phenotypes. These results demonstrate how reactive astrocytes modulate neurodegeneration, significantly contributing to our understanding of a role for reactive astrocytes in neurodegenerative diseases.
期刊介绍:
Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.