研究非人灵长类动物（NHP）的大脑对将啮齿动物研究转化到人类是必需的，但由于缺乏体外NHP大脑系统，分子、细胞和电路水平分析仍然是一个挑战。在这里，我们报告了使用卡利文金丝猴（Callithrix jacchus）胚胎干细胞衍生的神经结构组织（CAs）构建的体外 NHP 大脑模型，可以重现抑制性神经元迁移和皮层网络活动。从卡利文金丝猴胚胎干细胞诱导出皮层外形体和神经突起囊，它们融合形成了 CAs。表达抑制性神经元标记物 LHX6 的神经突起囊细胞向 CAs 的皮层侧迁移。随着皮层外形体的成熟，它们的自发神经活动从同步模式转变为不同步模式。包含兴奋性和抑制性神经元的 CAs 显示成熟的神经活动，其呈现出一种不同步的模式。该体外模型可用于研究兴奋性和抑制性神经元之间的相互作用、皮层动态以及它们的失调。卡利文金丝猴神经结构组织系统将为 NHP 神经生物学提供一个体外平台，并促进在神经科学研究、再生医学和药物发现方面向人类的转化。版权所有©2023 Elsevier Inc.。

Studying the non-human primate (NHP) brain is required for the translation of rodent research to humans, but remains a challenge for molecular, cellular, and circuit-level analyses in the NHP brain due to the lack of in vitro NHP brain system. Here, we report an in vitro NHP cerebral model using marmoset (Callithrix jacchus) embryonic stem cell-derived cerebral assembloids (CAs) that recapitulate inhibitory neuron migration and cortical network activity. Cortical organoids (COs) and ganglionic eminence organoids (GEOs) were induced from cjESCs and fused to generate CAs. GEO cells expressing the inhibitory neuron marker LHX6 migrated toward the cortical side of CAs. COs developed their spontaneous neural activity from a synchronized pattern to an unsynchronized pattern as COs matured. CAs containing excitatory and inhibitory neurons showed mature neural activity with an unsynchronized pattern. The CAs represent a powerful in vitro model for studying excitatory and inhibitory neuron interactions, cortical dynamics, and their dysfunction. The marmoset assembloid system will provide an in vitro platform for the NHP neurobiology and facilitate translation into humans in neuroscience research, regenerative medicine, and drug discovery.Copyright © 2023 Elsevier Inc. All rights reserved.