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Taking Cellular Heterogeneity Into Consideration When Modeling Astrocyte Involvement in Amyotrophic Lateral Sclerosis Using Human Induced Pluripotent Stem Cells
Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2021-09-17 , DOI: 10.3389/fncel.2021.707861
Stefano Stifani 1
Affiliation  

Astrocytes are a large group of glial cells that perform a variety of physiological functions in the nervous system. They provide trophic, as well as structural, support to neuronal cells. Astrocytes are also involved in neuroinflammatory processes contributing to neuronal dysfunction and death. Growing evidence suggests important roles for astrocytes in non-cell autonomous mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Understanding these mechanisms necessitates the combined use of animal and human cell-based experimental model systems, at least in part because human astrocytes display a number of unique features that cannot be recapitulated in animal models. Human induced pluripotent stem cell (hiPSC)-based approaches provide the opportunity to generate disease-relevant human astrocytes to investigate the roles of these cells in ALS. These approaches are facing the growing recognition that there are heterogenous populations of astrocytes in the nervous system which are not functionally equivalent. This review will discuss the importance of taking astrocyte heterogeneity into consideration when designing hiPSC-based strategies aimed at generating the most informative preparations to study the contribution of astrocytes to ALS pathophysiology.



中文翻译:

使用人诱导多能干细胞模拟星形胶质细胞参与肌萎缩侧索硬化时考虑细胞异质性

星形胶质细胞是一大群神经胶质细胞,在神经系统中执行多种生理功能。它们为神经元细胞提供营养和结构支持。星形胶质细胞也参与导致神经元功能障碍和死亡的神经炎症过程。越来越多的证据表明星形胶质细胞在肌萎缩侧索硬化 (ALS) 运动神经元变性的非细胞自主机制中发挥重要作用。了解这些机制需要结合使用基于动物和人类细胞的实验模型系统,至少部分是因为人类星形胶质细胞显示出许多无法在动物模型中重现的独特特征。基于人类诱导多能干细胞 (hiPSC) 的方法为生成与疾病相关的人类星形胶质细胞以研究这些细胞在 ALS 中的作用提供了机会。这些方法正面临越来越多的认识,即神经系统中存在功能不同的异质星形胶质细胞群。本综述将讨论在设计基于 hiPSC 的策略时考虑星形胶质细胞异质性的重要性,该策略旨在生成最有用的制剂来研究星形胶质细胞对 ALS 病理生理学的贡献。

更新日期:2021-09-17
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