Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids
Modeling the marmoset brain using embryonic stem cell-derived cerebral assembloids
复制标题
使用胚胎干细胞衍生的大脑组合体模拟狨猴大脑
DOI：
10.1016/j.bbrc.2023.03.019
复制
发表时间：
2023
影响因子：
3.1
通讯作者：
Fumitaka Osakada
中科院分区：
文献类型：
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作者：
Tomoki Kodera;Ryosuke F. Takeuchi;Sara Takahashi;Keiichiro Suzuki;Hidetoshi Kassai;Atsu Aiba;Seiji Shiozawa;Hideyuki Okano;Fumitaka Osakada
研究非人类灵长类动物 (NHP) 大脑是将啮齿动物研究转化为人类所必需的，但由于缺乏体外 NHP 大脑系统，对 NHP 大脑进行分子、细胞和电路水平分析仍然是一个挑战。在这里，我们报告了使用狨猴（Callithrix jacchus）胚胎干细胞衍生的大脑组合体（CA）的体外NHP大脑模型，该模型概括了抑制性神经元迁移和皮质网络活动。皮质类器官 (CO) 和神经节隆起类器官 (GEO) 由 cjESC 诱导并融合生成 CA。表达抑制性神经元标记物 LHX6 的 GEO 细胞向 CA 的皮质侧迁移。随着 CO 的成熟，CO 的自发神经活动从同步模式发展为不同步模式。含有兴奋性和抑制性神经元的 CA 显示出具有不同步模式的成熟神经活动。 CA 代表了一个强大的体外模型，用于研究兴奋性和抑制性神经元相互作用、皮质动力学及其功能障碍。狨猴组装体系统将为 NHP 神经生物学提供体外平台，并促进神经科学研究、再生医学和药物发现在人类中的转化。
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 ofin vitroNHP brain system. Here, we report anin vitroNHP 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 powerfulin vitromodel for studying excitatory and inhibitory neuron interactions, cortical dynamics, and their dysfunction. The marmoset assembloid system will provide anin vitroplatform for the NHP neurobiology and facilitate translation into humans in neuroscience research, regenerative medicine, and drug discovery.