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Tools and approaches for analyzing the role of mitochondria in health, development and disease using human cerebral organoids
Developmental Neurobiology ( IF 2.7 ) Pub Date : 2021-03-16 , DOI: 10.1002/dneu.22818
Michał Liput 1 , Chiara Magliaro 2 , Zuzanna Kuczynska 1 , Valery Zayat 1 , Arti Ahluwalia 2 , Leonora Buzanska 1
Affiliation  

Mitochondria are cellular organelles involved in generating energy to power various processes in the cell. Although the pivotal role of mitochondria in neurogenesis was demonstrated (first in animal models), very little is known about their role in human embryonic neurodevelopment and its pathology. In this respect human-induced pluripotent stem cells (hiPSC)-derived cerebral organoids provide a tractable, alternative model system of the early neural development and disease that is responsive to pharmacological and genetic manipulations, not possible to apply in humans. Although the involvement of mitochondria in the pathogenesis and progression of neurodegenerative diseases and brain dysfunction has been demonstrated, the precise role they play in cell life and death remains unknown, compromising the development of new mitochondria-targeted approaches to treat human diseases. The cerebral organoid model of neurogenesis and disease in vitro provides an unprecedented opportunity to answer some of the most fundamental questions about mitochondrial function in early human neurodevelopment and neural pathology. Largely an unexplored territory due to the lack of tools and approaches, this review focuses on recent technological advancements in fluorescent and molecular tools, imaging systems, and computational approaches for quantitative and qualitative analyses of mitochondrial structure and function in three-dimensional cellular assemblies—cerebral organoids. Future developments in this direction will further facilitate our understanding of the important role or mitochondrial dynamics and energy requirements during early embryonic development. This in turn will provide a further understanding of how dysfunctional mitochondria contribute to disease processes.

中文翻译:

使用人脑类器官分析线粒体在健康、发育和疾病中的作用的工具和方法

线粒体是细胞器,参与产生能量以驱动细胞中的各种过程。尽管证明了线粒体在神经发生中的关键作用(首先在动物模型中),但对它们在人类胚胎神经发育及其病理学中的作用知之甚少。在这方面,人类诱导的多能干细胞 (hiPSC) 衍生的脑类器官提供了一种易于处理的、替代的早期神经发育和疾病模型系统,该模型系统对药理学和基因操作有反应,不可能应用于人类。尽管已经证明线粒体参与神经退行性疾病和脑功能障碍的发病机制和进展,但它们在细胞生死中发挥的确切作用仍然未知,损害治疗人类疾病的新线粒体靶向方法的开发。体外神经发生和疾病的脑类器官模型提供了一个前所未有的机会来回答一些关于早期人类神经发育和神经病理学中线粒体功能的最基本问题。由于缺乏工具和方法,这在很大程度上是一个未开发的领域,本综述重点关注荧光和分子工具、成像系统和计算方法的最新技术进步,用于对 3D 细胞组装中线粒体结构和功能进行定量和定性分析——大脑类器官。这个方向的未来发展将进一步促进我们对早期胚胎发育过程中的重要作用或线粒体动力学和能量需求的理解。这反过来将进一步了解功能失调的线粒体如何导致疾病过程。
更新日期:2021-03-16
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