مورد إلكتروني

Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer's disease

التفاصيل البيبلوغرافية
العنوان: Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer's disease
المؤلفون: Guttikonda, S.R., Sikkema, L., Tchieu, J., Saurat, N., Walsh, R.M., Harschnitz, O., Ciceri, G., Sneeboer, M., Mazutis, L., Setty, M., Zumbo, P., Betel, D., Witte, L.D. de, Pe'er, D., Studer, L.
المصدر: Nature Neuroscience; 343; 354; 1097-6256; 3; 24; ~Nature Neuroscience~343~354~~~1097-6256~3~24~~
بيانات النشر: 2021
نوع الوثيقة: Electronic Resource
مستخلص: Contains fulltext : 244608.pdf (Publisher’s version ) (Closed access)
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 APP(SWE)+/+ 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 APP(SWE)+/+ 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.
URL: https://repository.ubn.ru.nl/handle/2066/244608
https://doi.org/10.1038/s41593-020-00796-z
الإتاحة: Open access content. Open access content
أرقام أخرى: NLQGE oai:repository.ubn.ru.nl:2066/244608
1292975809
المصدر المساهم: RADBOUD UNIVERSITEIT NAJMEGEN
From OAIster®, provided by the OCLC Cooperative.
رقم الأكسشن: edsoai.on1292975809
قاعدة البيانات: OAIster