iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases.
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DOI：
10.1016/j.neuron.2017.03.042
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发表时间：
2017-04-19
期刊：
影响因子：
16.2
通讯作者：
Blurton-Jones M
中科院分区：
文献类型：
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作者：
Abud EM;Ramirez RN;Martinez ES;Healy LM;Nguyen CHH;Newman SA;Yeromin AV;Scarfone VM;Marsh SE;Fimbres C;Caraway CA;Fote GM;Madany AM;Agrawal A;Kayed R;Gylys KH;Cahalan MD;Cummings BJ;Antel JP;Mortazavi A;Carson MJ;Poon WW;Blurton-Jones M
小胶质细胞在脑发育、动态平衡和神经紊乱中起着关键作用。在这里，我们报道了人类小胶质样细胞(IMGL)可以从IPSCs分化出来，以研究它们在阿尔茨海默病(AD)等神经系统疾病中的功能。我们发现iMGL在体外的发育类似于体内的小胶质细胞，整个转录组分析表明它们与培养的成人和胎儿小胶质细胞高度相似。对iMGL的功能评估表明，它们在炎症刺激下分泌细胞因子，迁移和经历钙瞬变，并强烈吞噬中枢神经系统底物。用IMGL检测Aβ纤维和脑源性tau寡聚体对AD相关基因表达的影响，并询问涉及突触修剪的机制。此外，将iMGLS移植到转基因小鼠和人脑组织中，在体内类似于小胶质细胞。综上所述，这些发现表明，iMGL可以用于研究小胶质细胞的功能，为人类神经疾病提供了重要的新见解。
Microglia play critical roles in brain development, homeostasis, and neurological disorders. Here, we report that human microglial-like cells (iMGL) can be differentiated from iPSCs to study their function in neurological diseases, like Alzheimer’s disease (AD). We find that iMGLs develop in vitro similarly to microglia in vivo and whole transcriptome analysis demonstrates that they are highly similar to cultured adult and fetal human microglia. Functional assessment of iMGLs reveals that they secrete cytokines in response to inflammatory stimuli, migrate and undergo calcium transients, and robustly phagocytose CNS substrates. iMGLs were used to examine the effects of Aβ fibrils and brain-derived tau oligomers on AD-related gene expression and to interrogate mechanisms involved in synaptic pruning. Furthermore, iMGLs transplanted into transgenic mice and human brain organoids resemble microglia in vivo. Together, these findings demonstrate that iMGLs can be used to study microglial function, providing important new insight into human neurological disease.