小柯机器人

美国斯隆·凯特琳癌症研究所Lorenz Studer小组发现，新型三元培养系统可模拟阿尔茨海默氏病的C3产生 。这一研究成果于2021年2月8日在线发表在国际学术期刊《自然—神经科学》上。

研究人员开发了一种从人类多能干细胞（hPSC）衍生小胶质细胞的新方法，并建立了一个明确的hPSC衍生的三元培养系统，其中包含hPSC衍生的小胶质细胞、星形胶质细胞和神经元，这个系统能够在体外根据神经炎症信号轴解析细胞互作。研究人员使用三元培养系统对带有APP^SWE+/+突变及其同基因控制的hPSC在阿尔茨海默氏病中的神经炎症进行建模。

研究人员发现补体C3是一种在炎症条件下增加并涉及突触丢失的蛋白，其在三元培养中被强化，而在APP^SWE+/+三元培养中由于小胶质细胞开始与星形胶质细胞产生相互的信号传递，从而产生过量的C3而被进一步增强。这项研究确定了导致阿尔茨海默氏病C3增加的主要细胞因子，并为研究人类疾病中的神经炎症提供了广泛适用的平台。 

据悉，中枢神经系统的异常炎症已被认为是人类神经退行性疾病发病机理的主要参与者。

附：英文原文

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

Author: Sudha R. Guttikonda, Lisa Sikkema, Jason Tchieu, Nathalie Saurat, Ryan M. Walsh, Oliver Harschnitz, Gabriele Ciceri, Marjolein Sneeboer, Linas Mazutis, Manu Setty, Paul Zumbo, Doron Betel, Lot D. de Witte, Dana Peer, Lorenz Studer

Issue&Volume: 2021-02-08

Abstract: 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.

DOI: 10.1038/s41593-020-00796-z

Source: https://www.nature.com/articles/s41593-020-00796-z

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex