Brain organoids: an ensemble of bioassays to investigate human neurodevelopment and disease.,Cell Death and Differentiation

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Brain organoids: an ensemble of bioassays to investigate human neurodevelopment and disease.
Cell Death and Differentiation ( IF 13.7 ) Pub Date : 2020-06-01 , DOI: 10.1038/s41418-020-0566-4
Jaydeep Sidhaye ₁ , Jürgen A Knoblich ₁

Affiliation

Abstract

Understanding etiology of human neurological and psychiatric diseases is challenging. Genomic changes, protracted development, and histological features unique to human brain development limit the disease aspects that can be investigated using model organisms. Hence, in order to study phenotypes associated with human brain development, function, and disease, it is necessary to use alternative experimental systems that are accessible, ethically justified, and replicate human context. Human pluripotent stem cell (hPSC)-derived brain organoids offer such a system, which recapitulates features of early human neurodevelopment in vitro, including the generation, proliferation, and differentiation of neural progenitors into neurons and glial cells and the complex interactions among the diverse, emergent cell types of the developing brain in three-dimensions (3-D). In recent years, numerous brain organoid protocols and related techniques have been developed to recapitulate aspects of embryonic and fetal brain development in a reproducible and predictable manner. Altogether, these different organoid technologies provide distinct bioassays to unravel novel, disease-associated phenotypes and mechanisms. In this review, we summarize how the diverse brain organoid methods can be utilized to enhance our understanding of brain disorders.

Facts

Brain organoids offer an in vitro approach to study aspects of human brain development and disease.
Diverse brain organoid techniques offer bioassays to investigate new phenotypes associated with human brain disorders that are difficult to study in monolayer cultures.
Brain organoids have been particularly useful to study phenomena and diseases associated with neural progenitor morphology, survival, proliferation, and differentiation.

Open question

Future brain organoid research needs to aim at later stages of neurodevelopment, linked with neuronal activity and connections, to unravel further disease-associated phenotypes.
Continued improvement of existing organoid protocols is required to generate standardized methods that recapitulate in vivo-like spatial diversity and complexity.

中文翻译：

脑类器官：研究人类神经发育和疾病的生物测定组合。

摘要

了解人类神经和精神疾病的病因学具有挑战性。人类大脑发育特有的基因组变化、长期发育和组织学特征限制了可以使用模型生物体研究的疾病方面。因此，为了研究与人类大脑发育、功能和疾病相关的表型，有必要使用易于使用、在伦理上合理且复制人类环境的替代实验系统。人类多能干细胞 (hPSC) 来源的大脑类器官提供了这样一个系统，它在体外重现了早期人类神经发育的特征，包括神经祖细胞的生成、增殖和分化为神经元和神经胶质细胞，以及不同的、三维（3-D）发育中大脑的新兴细胞类型。近年来，已经开发了许多脑类器官方案和相关技术，以可重复和可预测的方式概括胚胎和胎儿大脑发育的各个方面。总而言之，这些不同的类器官技术提供了不同的生物测定来揭示与疾病相关的新表型和机制。在这篇综述中，我们总结了如何利用不同的脑类器官方法来增强我们对脑部疾病的理解。