Generation of Functional Human 3D Cortico-Motor Assembloids.
Generation of Functional Human 3D Cortico-Motor Assembloids.
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DOI：
10.1016/j.cell.2020.11.017
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发表时间：
2020-12-23
期刊：
影响因子：
64.5
通讯作者：
Paşca SP
中科院分区：
文献类型：
--
作者：
Andersen J;Revah O;Miura Y;Thom N;Amin ND;Kelley KW;Singh M;Chen X;Thete MV;Walczak EM;Vogel H;Fan HC;Paşca SP
大脑皮层中的神经元通过下行通路连接到后脑和脊髓，以激活肌肉并产生运动。虽然这种通路的组成部分以前已经在体外产生和研究，但这种多突触回路的组装尚未在人类细胞中实现。在这里，我们得到类似于大脑皮层或后脑/脊髓的类器官，并将它们与人类骨骼肌球体组装在一起，以生成3D皮质运动类神经元。使用狂犬病示踪，钙成像，膜片钳记录，我们表明，离皮质神经元的项目和连接与脊髓球状体，而脊髓衍生的运动神经元连接肌肉。皮质球状体的谷氨酸释放或光遗传学刺激触发3D肌肉的强烈收缩，并且球状体在融合后长达10周的时间内在形态和功能上是完整的。总之，该系统突出了3D培养物形成可用于理解发育和疾病的功能电路的显着自组装能力。源自类似于大脑皮层、后脑/脊髓和骨骼肌的hiPS细胞的3D培养物的组装形成神经回路，其可以容易地操纵以在体外长期模拟肌肉收缩的皮层控制。
Neurons in the cerebral cortex connect through descending pathways to hindbrain and spinal cord to activate muscle and generate movement. Although components of this pathway have been previously generated and studied in vitro, the assembly of this multi-synaptic circuit has not yet been achieved with human cells. Here, we derive organoids resembling the cerebral cortex or the hindbrain/spinal cord and assemble them with human skeletal muscle spheroids to generate 3D cortico-motor assembloids. Using rabies tracing, calcium imaging, and patch-clamp recordings, we show that corticofugal neurons project and connect with spinal spheroids, while spinal-derived motor neurons connect with muscle. Glutamate uncaging or optogenetic stimulation of cortical spheroids triggers robust contraction of 3D muscle, and assembloids are morphologically and functionally intact for up to 10 weeks post-fusion. Together, this system highlights the remarkable self-assembly capacity of 3D cultures to form functional circuits that could be used to understand development and disease. The assembly of 3D cultures derived from hiPS cells resembling cerebral cortex, hindbrain/spinal cord, and skeletal muscle form neural circuits that can be readily manipulated to model cortical control of muscle contraction in vitro long term.
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影响因子：
82.9
作者：
Kaiser T;Feng G
通讯作者：
Feng G
影响因子：
16.2
作者：
Garden GA;La Spada AR
通讯作者：
La Spada AR
影响因子：
25
作者：
Cregg JM;Leiras R;Montalant A;Wanken P;Wickersham IR;Kiehn O
通讯作者：
Kiehn O
影响因子：
4.6
作者：
Duval, Nathalie;Vaslin, Celia;Ribes, Vanessa C.
通讯作者：
Ribes, Vanessa C.
DOI：
10.1038/nrn.2016.9
发表时间：
2016-04
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Kiehn O
通讯作者：
Kiehn O