浙江大学徐鹏飞团队的一项最新研究发现了用合成组织者建立人神经管类器官的背-腹模式。相关论文于2025年5月14日发表在《细胞—干细胞》杂志上。

该课题组介绍了来自多能干细胞聚集体（“ORDER”）的组织者，这是一种在神经外胚层细胞聚集体中建立相反的BMP和SHH梯度的方法。利用这种方法，该团队从斑马鱼和人类多能干细胞（hPSCs）中生成了具有有序D-V模式的NT类器官。单细胞转录组学分析显示，合成的人类NT类器官（hNTOs）与卡内基12期（CS12）的人类胚胎脊髓非常相似，并且与人类NT的相似性大于与motheme模型的相似性。

此外，通过hNTO模型，研究人员证明了WNT信号在调节中间祖细胞中的关键作用，模拟了TCTN2相关的D-V模式缺陷，并确定了一种补救策略。

研究人员表示，神经管（NT）的精确背腹（D-V）模式对中枢神经系统的发育和功能至关重要。然而，研究NT-D-V模式和相关人类疾病的现有模型仍然不足。

附：英文原文

Title: Establishing dorsal-ventral patterning in human neural tube organoids with synthetic organizers

Author: Tao Luo, Cong Liu, Tao Cheng, Guo-Qin Zhao, Ying Huang, Jing-Yun Luan, Junyu Guo, Xiang Liu, Yi-Fan Wang, Yang Dong, Yu Xiao, Enhui He, Rui-Zhen Sun, Xiuyu Chen, Jiekai Chen, Jun Ma, Sean Megason, Junfeng Ji, Peng-Fei Xu

Issue&Volume: 2025-05-14

Abstract: Precise dorsal-ventral (D-V) patterning of the neural tube (NT) is essential for the development and function of the central nervous system. However, existing models for studying NT D-V patterning and related human diseases remain inadequate. Here, we present organizers derived from pluripotent stem cell aggregate fusion (“ORDER”), a method that establishes opposing BMP and SHH gradients within neural ectodermal cell aggregates. Using this approach, we generated NT organoids with ordered D-V patterning from both zebrafish and human pluripotent stem cells (hPSCs). Single-cell transcriptomic analysis revealed that the synthetic human NT organoids (hNTOs) closely resemble the human embryonic spinal cord at Carnegie stage 12 (CS12) and exhibit greater similarity to human NT than to mouse models. Furthermore, using the hNTO model, we demonstrated the critical role of WNT signaling in regulating intermediate progenitors, modeled TCTN2-related D-V patterning defects, and identified a rescue strategy.

DOI: 10.1016/j.stem.2025.04.011

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00178-X