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自组织3D人躯干神经肌肉类器官体问世
作者:小柯机器人 发布时间:2020/1/19 14:43:01

德国马克斯·德尔布吕克分子医学中心Mina Gouti团队在研究中取得进展,他们开发出自组织的三维人体躯干神经肌肉器官体。该项研究成果于2020年1月16日在线发表在《细胞—干细胞》杂志上。

研究人员使用人多能干细胞(hPSC)来源的轴向干细胞(后体的构建基块)同时生成自组织的脊髓神经元和骨骼肌细胞,从而生成可以在3D模式下维持几个月的人类神经肌肉类器官体(NMO)。单个类器官体的单细胞RNA测序揭示了整个实验的可重复性,并且随着类器官体的发育和成熟,能够追踪神经和中胚层分化的轨迹。NMO包含末端施旺细胞支持的功能性神经肌肉接头。NMO收缩并发育出中枢模式发生器样神经元回路。
 
最后,研究人员成功地使用NMO来描绘了重症肌无力病理学的关键方面,从而强调了NMO在将来建模神经肌肉疾病方面的巨大潜力。
 
据介绍,神经肌肉网络在人类早期胚胎发育过程中组装,对于控制身体运动至关重要。以往研究中使用hPSC进行神经肌肉连接建模的工作是在单层培养中产生脊髓神经元或骨骼肌。
 
附:英文原文

Title: Self-Organizing 3D Human Trunk Neuromuscular Organoids

Author: Jorge-Miguel Faustino Martins, Cornelius Fischer, Alessia Urzi, Ramon Vidal, Severine Kunz, Pierre-Louis Ruffault, Loreen Kabuss, Iris Hube, Elisabeta Gazzerro, Carmen Birchmeier, Simone Spuler, Sascha Sauer, Mina Gouti

Issue&Volume: January 16, 2020

Abstract: Neuromuscular networks assemble during early human embryonic development and are essentialfor the control of body movement. Previous neuromuscular junction modeling effortsusing human pluripotent stem cells (hPSCs) generated either spinal cord neurons orskeletal muscles in monolayer culture. Here, we use hPSC-derived axial stem cells,the building blocks of the posterior body, to simultaneously generate spinal cordneurons and skeletal muscle cells that self-organize to generate human neuromuscularorganoids (NMOs) that can be maintained in 3D for several months. Single-cell RNA-sequencingof individual organoids revealed reproducibility across experiments and enabled the tracking of the neural and mesodermal differentiation trajectories as organoids developedand matured. NMOs contain functional neuromuscular junctions supported by terminalSchwann cells. They contract and develop central pattern generator-like neuronal circuits.Finally, we successfully use NMOs to recapitulate key aspects of myasthenia gravispathology, thus highlighting the significant potential of NMOs for modeling neuromuscular diseases in the future.

DOI: 10.1016/j.stem.2019.12.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30525-9

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx