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Cell diversity and network dynamics in photosensitive human brain organoids

机译：光敏性人脑类器官中的细胞多样性和网络动力学

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摘要

In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.
机译：发育中的大脑的体外模型（例如三维大脑类器官）为研究人脑发育和疾病的各个方面提供了前所未有的机会。然而，在类器官内产生的细胞以及它们在多大程度上概括了大脑的区域复杂性，细胞多样性和电路功能尚不清楚。在这里，我们分析了从31个人脑类器官分离的80,000多个个体细胞中的基因表达。我们发现类器官可以产生与内源性类别相关的多种细胞，包括来自大脑皮层和视网膜的细胞。类器官可以在较长的时间内（超过9个月）发育，从而可以建立相对成熟的特征，包括形成树突棘和自发活跃的神经元网络。最后，可以使用光敏细胞的光刺激来控制类器官内的神经元活动，这可以提供一种使用生理感觉刺激来探测人神经元回路功能的方法。

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  • 来源
    《Nature》 |2017年第7652期|48-53|共6页
  • 作者

    Quadrato Giorgia; Tuan Nguyen; Macosko Evan Z.; Sherwood John L.; Yang Sung Min; Berger Daniel R.; Maria Natalie; Scholvin Jorg; Goldman Melissa; Kinney Justin P.; Boyden Edward S.; Lichtman Jeff W.; Williams Ziv M. .; McCarroll Steven A.; Arlotta Paola;

  • 作者单位

    Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA|Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;

    Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA|Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;

    Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA|Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA|Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;

    Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA;

    Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA|Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA;

    Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA;

    MIT, Dept Biol Engn, MIT Media Lab, Cambridge, MA 02139 USA|MIT, Dept Brain & Cognit Sci, MIT Media Lab, Cambridge, MA 02139 USA|MIT, McGovern Inst, Cambridge, MA 02139 USA;

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    LeafLabs LLC, Cambridge, MA 02139 USA;

    MIT, Dept Biol Engn, MIT Media Lab, Cambridge, MA 02139 USA|MIT, Dept Brain & Cognit Sci, MIT Media Lab, Cambridge, MA 02139 USA|MIT, McGovern Inst, Cambridge, MA 02139 USA;

    Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA|Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA;

    Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA;

    Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA|Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA|Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA;

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