相关实验视频

Updated: Sep 12, 2025

Establishment of an Electrophysiological Platform for Modeling ALS with Regionally-Specific Human Pluripotent Stem Cell-Derived Astrocytes and Neurons

Establishment of an Electrophysiological Platform for Modeling ALS with Regionally-Specific Human Pluripotent Stem Cell-Derived Astrocytes and Neurons

Published on: August 26, 2021

在使用微流体装置的iPSC衍生ALS细胞模型中研究早期轴突表型

Asako Otomo^1,2, Keiko Nishijima¹, Yuta Murakami³

¹Molecular Neuropathobiology Laboratory, Department of Physiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

Frontiers in cellular neuroscience

|August 8, 2025

概括

这项研究开发了一种微流体装置,使用患者衍生的神经元来模拟肌缩性侧面硬化症 (ALS). 该设备揭示了FUS突变神经元中的早期轴突生长缺陷和线粒体运输问题,有助于ALS研究.

科学领域:

神经科学是一个神经科学.
干细胞生物学干细胞生物学
生物医学工程生物医学工程

背景情况:

肌缩侧面硬化症 (ALS) 是一种进展性神经退行性疾病,影响运动神经元.
FUS/TLS基因的突变是家族性ALS的常见原因.
来自ALS患者的诱导多能干细胞 (iPSC) 对研究神经退行有价值.

研究的目的:

开发和验证一种微流体装置,用于在iPSC衍生神经元中高分辨率观察轴突表型.
用微流体系统评估具有FUS/TLS突变的低运动神经元 (LMN) 中的神经退行性表型.
为了识别ALS中退化的早期细胞标志物.

主要方法:

从携带FUS/TLS突变 (FUS_H517D) 的iPSC产生下部运动神经元 (LMN).
使用一种新的微流体装置培养和观察神经元轴突生长,形态和贩运.
在不同的条件下评估细胞活力,轴突长度和线粒体运输.

主要成果:

由FUS突变的LMN显著减少了轴突长度,并通过DIV7损害了轴突生长,先于明显的细胞死亡.
与对照组相比,FUS突变LMN的细胞活力在DIV14和DIV21之间显著下降.
在FUS突变的LMN轴突中观察到运动性线粒体的增加和贩运模式的改变.

结论:

微流体装置有效地模拟了ALS早期轴突退化的模型.
轴突生长限制和线粒体运输变化是FUS突变神经元中早期可检测的表型.
这个系统为研究ALS轴突退化的分子机制提供了一个有价值的细胞模型.

关键词:

在FUS/TLS中使用.肌缩侧面硬化症 (ALS) 是一种疾病.这些是iPSCs.较低的运动神经元.微流体装置是一种微流体装置.

更多相关视频

In vitro Modeling for Neurological Diseases using Direct Conversion from Fibroblasts to Neuronal Progenitor Cells and Differentiation into Astrocytes

In vitro Modeling for Neurological Diseases using Direct Conversion from Fibroblasts to Neuronal Progenitor Cells and Differentiation into Astrocytes

Published on: June 10, 2021

Fabrication of a Microfluidic Device for the Compartmentalization of Neuron Soma and Axons

Fabrication of a Microfluidic Device for the Compartmentalization of Neuron Soma and Axons

Published on: August 22, 2007

相关概念视频

EPS and iPS Cells in Disease Research

EPS and iPS Cells in Disease Research

Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...