Wu Sih-Rong, Nowakowski Tomasz J
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Neuron. 2025 Apr 16;113(8):1133-1150. doi: 10.1016/j.neuron.2025.02.010. Epub 2025 Mar 18.
How the human brain develops and what goes awry in neurological disorders represent two long-lasting questions in neuroscience. Owing to the limited access to primary human brain tissue, insights into these questions have been largely gained through animal models. However, there are fundamental differences between developing mouse and human brain, and neural organoids derived from human pluripotent stem cells (hPSCs) have recently emerged as a robust experimental system that mimics self-organizing and multicellular features of early human brain development. Controlled integration of multiple organoids into assembloids has begun to unravel principles of cell-cell interactions. Moreover, patient-derived or genetically engineered hPSCs provide opportunities to investigate phenotypic correlates of neurodevelopmental disorders and to develop therapeutic hypotheses. Here, we outline the advances in technologies that facilitate studies by using assembloids and summarize their applications in brain development and disease modeling. Lastly, we discuss the major roadblocks of the current system and potential solutions.
人类大脑如何发育以及神经疾病中出现的问题是神经科学领域两个长期存在的问题。由于获取原发性人类脑组织的机会有限，对这些问题的深入了解主要是通过动物模型获得的。然而，发育中的小鼠大脑和人类大脑之间存在根本差异，源自人类多能干细胞（hPSCs）的神经类器官最近已成为一种强大的实验系统，可模拟人类早期大脑发育的自组织和多细胞特征。将多个类器官可控整合到组装体中已开始揭示细胞间相互作用的原理。此外，患者来源的或经过基因工程改造的hPSCs为研究神经发育障碍的表型相关性以及制定治疗假设提供了机会。在这里，我们概述了通过使用组装体促进研究的技术进展，并总结了它们在大脑发育和疾病建模中的应用。最后，我们讨论了当前系统的主要障碍和潜在解决方案。
