移植集合体中具有功能性脑皮层胆碱能投射的人基底核类器官的产生，这一成果由南京医科大学刘妍团队经过不懈努力而取得。2025年11月3日，国际知名学术期刊《细胞—干细胞》发表了这一成果。

课题组人员从含有功能性胆碱能投射神经元的人多能干细胞（hPSCs）中生成了人类nbM类器官（hnbMOs）。通过与人胎脑共培养，再将hnbMOs移植到免疫缺陷小鼠体内，重建了nbM向大脑皮层的远距离胆碱能投射。课题组研究人员通过将hnbMOs与人类皮质类器官（hCOs）结合，进一步建立了nbM-皮质组装体。该团队还在移植的集合体中建立了人类特异性的胆碱能投射系统。通过病毒追踪和功能分析，小组证实胆碱能神经元向hCOs发送投射并形成突触连接。

此外，研究人员在DS衍生的组装体中捕获了投射缺陷，证明了该模型在研究nbM相关的神经回路和神经系统疾病方面的实用性。

据了解，Meynert基底核（nbM）是基底前脑的主要胆碱能输出，调节皮质调节、学习和记忆。nbM-皮质胆碱能通路功能障碍与神经退行性和神经发育障碍有关，包括阿尔茨海默病（AD）和唐氏综合征（DS）。

附：英文原文

Title: Generation of human nucleus basalis organoids with functional nbM-cortical cholinergic projections in transplanted assembloids

Author: Da Wang, Xinyue Zhang, Xiao-Yan Tang, Yixia Gan, Hanwen Yu, Shanshan Wu, Yuan Hong, Mengdan Tao, Chu Chu, Xiaoxuan Qi, Hao Hu, Yimin Zhu, Wanying Zhu, Xiao Han, Min Xu, Yi Dong, Qing Cheng, Xing Guo, Yan Liu

Issue&Volume: 2025-11-03

Abstract: The nucleus basalis of Meynert (nbM), the major cholinergic output of the basal forebrain, regulates cortical modulation, learning, and memory. Dysfunction of the nbM-cortical cholinergic pathway is implicated in neurodegenerative and neurodevelopmental disorders, including Alzheimer’s disease (AD) and Down syndrome (DS). Here, we generated human nbM organoids (hnbMOs) from human pluripotent stem cells (hPSCs) containing functional cholinergic projection neurons. Then we reconstructed long-distance cholinergic projections from nbM to the cortex by co-culturing hnbMOs with human fetal brains and transplanting hnbMOs into immunodeficient mice. We further established nbM-cortical assembloids by fusing hnbMOs with human cortical organoids (hCOs). We also established a human-specific cholinergic projection system in transplanted assembloids. Using viral tracing and functional assays, we validated that cholinergic neurons send projections into hCOs and form synaptic connections. Moreover, we captured projection deficits in DS-derived assembloids, demonstrating the utility of this model for studying nbM-related neural circuits and neurological disorders.

DOI: 10.1016/j.stem.2025.10.004

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00372-8