2024年12月9日，上海科技大学向阳飞小组在《细胞—干细胞》杂志在线发表论文，其通过人类多能干细胞生成自组织的神经肌肉骨骼三组织类器官。

据了解，人体功能需要不同组织之间的相互交流，其中NMS轴是一个关键的相互作用，涉及神经、肌肉和骨骼组织，这在使用人类细胞进行建模时具有挑战性。

研究人员描述了通过共发育策略，从人类多能干细胞生成三维神经肌肉骨骼三组织类器官（hNMSO）。染色、单核RNA测序和空间转录组分析揭示了神经、肌肉和骨骼谱系，在单个类器官中的共同出现和自组织，并且hNMSO的神经区域获得了腹侧特异性身份，并产生了支配骨骼肌的运动神经元。

hNMSO的神经、肌肉和骨骼区域在发育过程中表现出成熟，并建立了功能连接。值得注意的是，结构、功能和转录组分析表明，hNMSO中的骨骼支撑有助于人类肌肉的发育。使用hNMSO的建模还揭示了病理性骨骼退化后的神经肌肉改变。总之，该研究提供了一个易于获取的实验模型，供未来研究人类NMS相互作用及其异常使用。

附：英文原文

Title: Generation of self-organized neuromusculoskeletal tri-tissue organoids from human pluripotent stem cells

Author: Yao Yin, Wei Zhou, Jinkui Zhu, Ziling Chen, Linlin Jiang, Xuran Zhuang, Jia Chen, Jianfeng Wei, Xiaoxiang Lu, Yantong Liu, Wei Pang, Qinzhi Zhang, Yajing Cao, Zhuoya Li, Yuyan Zhu, Yangfei Xiang

Issue&Volume: 2024-12-09

Abstract: The human body function requires crosstalk between different tissues. An essential crosstalk is in the neuromusculoskeletal (NMS) axis involving neural, muscular, and skeletal tissues, which is challenging to model using human cells. Here, we describe the generation of three-dimensional, NMS tri-tissue organoids (hNMSOs) from human pluripotent stem cells through a co-development strategy. Staining, single-nucleus RNA sequencing, and spatial transcriptome profiling revealed the co-emergence and self-organization of neural, muscular, and skeletal lineages within individual organoids, and the neural domains of hNMSOs obtained a ventral-specific identity and produced motor neurons innervating skeletal muscles. The neural, muscular, and skeletal regions of hNMSOs exhibited maturation and established functional connections during development. Notably, structural, functional, and transcriptomic analyses revealed that skeletal support in hNMSOs benefited human muscular development. Modeling with hNMSOs also unveiled the neuromuscular alterations following pathological skeletal degeneration. Together, our study provides an accessible experimental model for future studies of human NMS crosstalk and abnormality.

DOI: 10.1016/j.stem.2024.11.005

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00404-1