神经炎症
小胶质细胞
诱导多能干细胞
疾病
神经科学
细胞生物学
炎症
生物
免疫学
医学
胚胎干细胞
遗传学
基因
病理
作者
Sudha R. Guttikonda,Lisa Sikkema,Jason Tchieu,Nathalie Saurat,Ryan Walsh,Oliver Harschnitz,Gabriele Ciceri,Marjolein Sneeboer,Linas Mažutis,Manu Setty,Paul Zumbo,Doron Betel,Lot de Witte,Dana Pe’er,Lorenz Studer
标识
DOI:10.17504/protocols.io.btt9nnr6
摘要
Aberrant inflammation in the CNS has been implicated as a major player in the pathogenesis of human neurodegenerative disease. We developed a new approach to derive microglia from human pluripotent stem cells (hPSCs) and built a defined hPSC-derived tri-culture system containing pure populations of hPSC-derived microglia, astrocytes, and neurons to dissect cellular cross-talk along the neuroinflammatory axis in vitro. We used the tri-culture system to model neuroinflammation in Alzheimer’s disease with hPSCs harboring the APPSWE+/+ mutation and their isogenic control. We found that complement C3, a protein that is increased under inflammatory conditions and implicated in synaptic loss, is potentiated in tri-culture and further enhanced in APPSWE+/+ tri-cultures due to microglia initiating reciprocal signaling with astrocytes to produce excess C3. Our study defines the major cellular players contributing to increased C3 in Alzheimer’s disease and presents a broadly applicable platform to study neuroinflammation in human disease.
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