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科学家培养出功能性人类3D皮质-运动神经类组装体
作者:小柯机器人 发布时间:2020/12/18 21:45:37

近日,美国斯坦福大学Sergiu P. Paca及其研究小组培养出功能性人类3D皮质-运动神经类组装体。相关论文于2020年12月16日在线发表在《细胞》杂志上。

研究人员获得了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皮质运动类组装体。使用狂犬病毒追踪、钙成像和膜片钳记录,研究人员发现,皮质原位神经元投射并与脊髓球体相连,而脊髓衍生的运动神经元与肌肉相连。谷氨酸释放或光遗传刺激皮质球体会触发3D肌肉的强烈收缩,而类组装体在融合后长达10周内的形态和功能是完整的。

该系统共同强调了3D培养具有非凡的自组装能力,可形成可用于理解发育和疾病的功能性回路。

据介绍,大脑皮层中的神经元通过下行通路连接到后脑和脊髓,从而激活肌肉并产生运动。尽管该通路的成分先前已经产生并在体外进行了研究,但这种多突触回路的组装尚未通过人类细胞实现。

附:英文原文

Title: Generation of Functional Human 3D Cortico-Motor Assembloids

Author: Jimena Andersen, Omer Revah, Yuki Miura, Nicholas Thom, Neal D. Amin, Kevin W. Kelley, Mandeep Singh, Xiaoyu Chen, Mayuri Vijay Thete, Elisabeth M. Walczak, Hannes Vogel, H. Christina Fan, Sergiu P. Paca

Issue&Volume: 2020-12-16

Abstract: 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.

DOI: 10.1016/j.cell.2020.11.017

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31534-8

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/