Improved modeling of human AD with an automated culturing platform for iPSC neurons, astrocytes and microglia.
Improved modeling of human AD with an automated culturing platform for iPSC neurons, astrocytes and microglia.
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DOI：
10.1038/s41467-021-25344-6
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发表时间：
2021-09-01
影响因子：
16.6
通讯作者：
Chih B
中科院分区：
文献类型：
--
作者：
Bassil R;Shields K;Granger K;Zein I;Ng S;Chih B
人类诱导多能干细胞（iPSC）神经元和小胶质细胞分化方案的进展允许使用生理相关细胞进行疾病建模。然而，iPSC分化和培养方案对保持一致性提出了挑战。在这里，我们建立了一个自动化的、一致的、长期的人类iPSC神经元、星形胶质细胞和小胶质细胞培养平台。使用该平台，我们使用人源性细胞生成了iPSC AD模型，该模型在一个模型中显示出a β斑块、斑块周围神经突营养不良、突触丢失、树突缩回、轴突断裂、磷酸化- tau诱导和神经元细胞死亡的迹象。我们发现人类iPSC小胶质细胞内化并压缩了Aβ以产生和包围斑块，从而赋予了一些神经保护作用。我们研究了抗a β抗体保护的作用机制，发现它们保护神经元免受这些病理的影响，并且在pTau诱导之前最有效。综上所述，这些结果表明该模型可以促进靶点发现和药物开发工作。人类诱导多能干细胞（iPSC）细胞已被用于模拟特定细胞类型的疾病。在这里，作者开发了一个人类iPSC神经元、星形胶质细胞和小胶质细胞的自动长期培养平台，并用它来模拟阿尔茨海默病的一些细胞方面。
Advancement in human induced pluripotent stem cell (iPSC) neuron and microglial differentiation protocols allow for disease modeling using physiologically relevant cells. However, iPSC differentiation and culturing protocols have posed challenges to maintaining consistency. Here, we generated an automated, consistent, and long-term culturing platform of human iPSC neurons, astrocytes, and microglia. Using this platform we generated a iPSC AD model using human derived cells, which showed signs of Aβ plaques, dystrophic neurites around plaques, synapse loss, dendrite retraction, axon fragmentation, phospho-Tau induction, and neuronal cell death in one model. We showed that the human iPSC microglia internalized and compacted Aβ to generate and surround the plaques, thereby conferring some neuroprotection. We investigated the mechanism of action of anti-Aβ antibodies protection and found that they protected neurons from these pathologies and were most effective before pTau induction. Taken together, these results suggest that this model can facilitate target discovery and drug development efforts. Human induced pluripotent stem cell (iPSC) cells have been used to model disease in specific cell types. Here, the authors develop an automated long-term culturing platform of human iPSC neurons, astrocytes, and microglia and use it to model some cellular aspects of Alzheimer’s disease.
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影响因子：
4.6
作者：
Chen HH;Liu P;Auger P;Lee SH;Adolfsson O;Rey-Bellet L;Lafrance-Vanasse J;Friedman BA;Pihlgren M;Muhs A;Pfeifer A;Ernst J;Ayalon G;Wildsmith KR;Beach TG;van der Brug MP
通讯作者：
van der Brug MP
影响因子：
11.2
作者：
Kaufman, Adam C.;Salazar, Santiago V.;Haas, Laura T.;Yang, Jinhee;Kostylev, Mikhail A.;Jeng, Amanda T.;Robinson, Sophie A.;Gunther, Erik C.;van Dyck, Christopher H.;Nygaard, Haakon B.;Strittmatter, Stephen M.
通讯作者：
Strittmatter, Stephen M.
影响因子：
5.3
作者：
Larhammar, Martin;Huntwork-Rodriguez, Sarah;Lewcock, Joseph W.
通讯作者：
Lewcock, Joseph W.
影响因子：
5.9
作者：
Chanda, Soham;Ang, Cheen Euong;Davila, Jonathan;Pak, ChangHui;Mall, Moritz;Lee, Qian Yi;Ahlenius, Henrik;Jung, Seung Woo;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
16.2
作者：
Ashe, Karen H.;Zahs, Kathleen R.
通讯作者：
Zahs, Kathleen R.