Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells.
Generation of human striatal organoids and cortico-striatal assembloids from human pluripotent stem cells.
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DOI：
10.1038/s41587-020-00763-w
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发表时间：
2020-12
影响因子：
46.9
通讯作者：
Pasca, Sergiu P.
中科院分区：
文献类型：
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作者：
Miura, Yuki;Li, Min-Yin;Birey, Fikri;Ikeda, Kazuya;Revah, Omer;Thete, Mayuri Vijay;Park, Jin-Young;Puno, Alyssa;Lee, Samuel H.;Porteus, Matthew H.;Pasca, Sergiu P.
皮质纹状体投射是调节动机行为的前脑回路的关键组成部分。为了研究人类皮质纹状体通路及其功能障碍如何导致神经精神疾病，我们开发了一种将人类多能干细胞转化为区域特异性脑类器官的方法，该脑类器官类似于正在发育的人类纹状体，并包括电活性中等多棘神经元。然后，我们在三维培养物中将这些类器官与大脑皮质类器官组装起来，形成皮质纹状体组合体。通过对完整或切片的组合体进行病毒追踪和功能分析，我们发现皮质神经元将轴突投射发送到纹状体类器官并形成突触连接。中型多棘神经元在组装后电生理成熟，并在皮层神经元的光遗传学刺激后表现出钙活性。此外，我们从患有由染色体 22q13.3 缺失引起的神经发育障碍的患者中获得皮质纹状体组装体，并捕获与疾病相关的钙活性缺陷，表明这种方法将允许使用患者来源的细胞研究皮质纹状体连接的发育和功能组装。
Cortico-striatal projections are critical components of forebrain circuitry that regulate motivated behaviors. To enable the study of the human cortico-striatal pathway and how its dysfunction leads to neuropsychiatric disease, we developed a method to convert human pluripotent stem cells into region-specific brain organoids that resemble the developing human striatum and include electrically active medium spiny neurons. We then assembled these organoids with cerebral cortical organoids in three-dimensional cultures to form cortico-striatal assembloids. Using viral tracing and functional assays in intact or sliced assembloids, we show that cortical neurons send axonal projections into striatal organoids and form synaptic connections. Medium spiny neurons mature electrophysiologically following assembly and display calcium activity after optogenetic stimulation of cortical neurons. Moreover, we derive cortico-striatal assembloids from patients with a neurodevelopmental disorder caused by a deletion on chromosome 22q13.3 and capture disease-associated defects in calcium activity, showing that this approach will allow investigation of the development and functional assembly of cortico-striatal connectivity using patient-derived cells.
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影响因子：
16.2
作者：
Lieberman OJ;McGuirt AF;Mosharov EV;Pigulevskiy I;Hobson BD;Choi S;Frier MD;Santini E;Borgkvist A;Sulzer D
通讯作者：
Sulzer D
影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
64.8
作者：
通讯作者：
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影响因子：
2.5
作者：
Belleau, ML;Warren, RA
通讯作者：
Warren, RA
DOI：
10.1038/mtna.2014.64
发表时间：
2014-12-02
期刊：
Molecular therapy. Nucleic acids
影响因子：
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作者：
通讯作者：
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