Highly efficient induction of functionally mature excitatory neurons from feeder-free human ES/iPS cells
Highly efficient induction of functionally mature excitatory neurons from feeder-free human ES/iPS cells
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从无饲养层人 ES/iPS 细胞中高效诱导功能成熟的兴奋性神经元
DOI：
10.1101/2023.02.10.528087
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Okano Hideyuki
中科院分区：
文献类型：
--
作者：
Zhou Zhi;Kakegawa Wataru;Fujimori Koki;Sho Misato;Shimamura Rieko;Supakul Sopak;Yoshimatsu Sho;Kohyama Jun;Yuzaki Michisuke;Okano Hideyuki
皮层兴奋性神经元（Cx神经元）是大脑皮层中最主要的神经元细胞类型，在认知、知觉、智力行为和情绪加工中起着重要作用。强抑素体外诱导Cx神经元可能有助于阐明包括阿尔茨海默病在内的顽固性神经发育和神经退行性疾病的脑发育和病理机制，从而可能有助于药物开发。在这里，我们报告了一种确定的方法，可以有效地从无饲料条件的人胚胎干细胞（ES细胞）和诱导多能干细胞（iPS细胞）中诱导Cx神经元。利用该方法，人ES/iPS细胞在3周内可分化为~99%的map2阳性神经元，在5周内，这些诱导神经元表现出谷氨酸能神经元特异性标志物（AMPA、NDMA受体亚基和CAMKIIα）的强烈表达、高度同步的自发放电和兴奋性突触后电流（EPSC）等成熟兴奋性神经元的多种特征。此外，Cx神经元对a β42寡聚物的毒性和过量谷氨酸的兴奋毒性表现出易感性，这在毒性试验和寻找治疗药物方面又具有优势。综上所述，本研究为基于无喂食人ES/iPS细胞系统的神经发育和退化研究提供了一个新的研究平台。
Cortical excitatory neurons (Cx neurons) are the most dominant neuronal cell type in the cerebral cortex, which play a central role in cognition, perception, intellectual behavior and emotional processing. Robustin vitroinduction of Cx neurons may facilitate as a tool for the elucidation of brain development and pathomechanism of the intractable neurodevelopmental and neurodegenerative disorders including Alzheimer’s disease, and thus potentially contribute to drug development. Here, we report a defined method for efficient induction of Cx neurons from the feeder-free-conditioned human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). By using this method, human ES/iPS cells could be differentiated into ~99% MAP2-positive neurons by three weeks, and these induced neurons, within five weeks, presented various characteristics of mature excitatory neurons such as strong expression of glutamatergic neuron-specific markers (subunits of AMPA and NDMA receptors and CAMKIIα), highly synchronized spontaneous firing and excitatory postsynaptic current (EPSC). Moreover, the Cx neurons showed susceptibility to the toxicity of Aβ42oligomers and excitotoxicity of excessive glutamates, which is another advantage in terms of toxicity test and searching for the therapeutic agents. Taken together, this study provides a novel research platform for the study of neural development and degeneration based on the feeder-free human ES/iPS cell system.
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影响因子：
5.2
作者：
Okada, Yohei;Matsumoto, Arifumi;Okano, Hideyuki
通讯作者：
Okano, Hideyuki
类胡萝卜素的联合治疗通过抑制 β 分泌酶减少人类神经元中 Aβ 的分泌
影响因子：
2.9
作者：
Sho Misato;Ichiyanagi Naoki;Imaizumi Kent;Ishikawa Mitsuru;Morimoto Satoru;Watanabe Hirotaka;Okano Hideyuki
通讯作者：
Okano Hideyuki
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Tanabe, Koji;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
DOI：
10.1111/j.1469-7610.2010.02307.x
发表时间：
2011-04
期刊：
Journal of child psychology and psychiatry, and allied disciplines
影响因子：
--
作者：
Rubenstein JL
通讯作者：
Rubenstein JL
影响因子：
25
作者：
Watanabe, K;Kamiya, D;Sasai, Y
通讯作者：
Sasai, Y