Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output

Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output
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气液界面的大脑类器官产生具有功能输出的不同神经束

DOI:
10.1101/353151
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发表时间:
2018
期刊:
--
影响因子:
--
通讯作者:
Giandomenico S
Giandomenico S
中科院分区:
--
文献类型:
--
作者:
Giandomenico S

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神经类器官有可能提高我们对人类大脑发育和神经系统疾病的理解。然而,这些组织是否可以模拟具有功能性神经元输出的电路形成还有待观察。在这里,我们已经使空气-液体界面培养适应脑类器官,从而改善神经元存活和轴突生长。由此产生的粗轴突束显示各种形态,包括长距离投影内和远离类器官,生长锥转向,交叉。单细胞RNA测序揭示了各种皮质神经元的身份,逆行追踪表明道形态匹配适当的分子身份。这些文化表现出活跃的神经元网络,和皮质下投射束可以支配小鼠脊髓外植体,并引起收缩的方式依赖于完整的类器官来源的神经支配束相邻的肌肉。总的来说,这些结果揭示了一个显着的自我组织的离皮质和胼胝体束的功能输出,提供了新的机会来研究人类中枢神经系统的发展和疾病的相关方面。
Neural organoids have the potential to improve our understanding of human brain development and neurological disorders. However, it remains to be seen whether these tissues can model circuit formation with functional neuronal output. Here we have adapted air–liquid interface culture to cerebral organoids, leading to improved neuronal survival and axon outgrowth. The resulting thick axon tracts display various morphologies, including long-range projection within and away from the organoid, growth-cone turning, and decussation. Single-cell RNA sequencing reveals various cortical neuronal identities, and retrograde tracing demonstrates tract morphologies that match proper molecular identities. These cultures exhibit active neuronal networks, and subcortical projecting tracts can innervate mouse spinal cord explants and evoke contractions of adjacent muscle in a manner dependent on intact organoid-derived innervating tracts. Overall, these results reveal a remarkable self-organization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and disease.
DOI: 10.1101/159137
发表时间: 2017-07
期刊: bioRxiv
影响因子: --
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发表时间: 1988-11-01
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影响因子: 3.6
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