Comparative Multiomics Analysis of Cerebral Organoid-Derived Exosomes during Organoid Maturation

Cerebral organoids derived from human pluripotent stem
cells recapitulate
key features of early brain development and provide a physiologically
relevant model for neurogenesis. Exosomes secreted by these organoids
carry bioactive cargo and offer a noninvasive means to monitor maturation
and intercellular communication. We performed comprehensive multiomics
profiling of exosomes collected from cerebral organoids at defined
developmental stages to evaluate their utility as biomarkers of neuronal
differentiation. Metabolomic analysis revealed a progressive decline
in amino acids, including glutamic acid, consistent with increased
metabolic demand during neurogenesis. Lipidomic and neurosteroid profiling
showed dynamic increases in phosphatidylethanolamine and pregnenolone,
reflecting synaptic membrane formation and signaling. Transcriptomic
and proteomic analyses identified stage-specific neurodevelopmental
signatures, with key markers mirroring those of parent organoids.
Collectively, cerebral organoid-derived exosomes faithfully reflect
organoid maturation and provide a robust platform for tracking in
vitro brain development.

源自人类多能干细胞（human pluripotent stem cells）的大脑类器官（cerebral organoids）可重现早期脑发育的关键特征，并为神经发生提供生理相关的研究模型。此类类器官分泌的外泌体（exosomes）携带生物活性负载物，为监测类器官成熟过程与细胞间通讯提供了无创手段。本研究对特定发育阶段大脑类器官来源的外泌体开展了全面的多组学分析，以评估其作为神经元分化生物标志物的应用潜力。代谢组学分析显示，包括谷氨酸（glutamic acid）在内的氨基酸水平呈进行性下降，这与神经发生过程中代谢需求升高的现象一致。脂质组学与神经甾体谱分析结果显示，磷脂酰乙醇胺（phosphatidylethanolamine）和孕烯醇酮（pregnenolone）的水平呈动态升高，这反映了突触膜形成与信号传导过程。转录组学与蛋白质组学分析鉴定出了发育阶段特异性的神经发育特征，其关键标志物与亲本类器官的标志物高度一致。综上，大脑类器官来源的外泌体可真实反映类器官的成熟过程，并为追踪体外脑发育提供了可靠的研究平台。