Department of Neurology, University of California, San Francisco, CA, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA.
Department of Anatomy, University of California, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
Brain Res. 2019 Dec 15;1725:146470. doi: 10.1016/j.brainres.2019.146470. Epub 2019 Sep 19.
The brain is one of the most complex organs in the body, which emerges from a relatively simple set of basic 'building blocks' during early development according to complex cellular and molecular events orchestrated through a set of inherited instructions. Innovations in stem cell technologies have enabled modelling of neural cells using two- and three-dimensional cultures. In particular, cerebral ('brain') organoids have taken the center stage of brain development models that have the potential for providing meaningful insight into human neurodevelopmental and neurological disorders. We review the current understanding of cellular events during human brain organogenesis, and the events occurring during cerebral organoid differentiation. We highlight the strengths and weaknesses of this experimental model system. In particular, we explain evidence that organoids can mimic many aspects of early neural development, including neural induction, patterning, and broad neurogenesis and gliogenesis programs, offering the opportunity to study genetic regulation of these processes in a human context. Several shortcomings of the current culture methods limit the utility of cerebral organoids to spontaneously give rise to many important cell types, and to model higher order features of tissue organization. We suggest that future studies aim to improve these features in order to make them better models for the study of laminar organization, circuit formation and how disruptions of these processes relate to disease.
大脑是人体中最复杂的器官之一，根据一套通过遗传指令协调的复杂细胞和分子事件，从相对简单的基本“构建块”中早期发育而来。干细胞技术的创新使得使用二维和三维培养物来模拟神经细胞成为可能。特别是，大脑（“脑”）类器官已成为脑发育模型的中心舞台，有可能为人类神经发育和神经疾病提供有意义的见解。我们回顾了当前对人类大脑类器官发生过程中的细胞事件的理解，以及在大脑类器官分化过程中发生的事件。我们强调了这个实验模型系统的优缺点。特别是，我们解释了证据表明类器官可以模拟早期神经发育的许多方面，包括神经诱导、模式形成以及广泛的神经发生和神经胶质发生程序，从而有机会在人类背景下研究这些过程的遗传调控。目前的培养方法有几个缺点，限制了大脑类器官自发产生许多重要细胞类型的能力，也限制了其作为组织高级特征模型的应用。我们建议未来的研究旨在改进这些特性，以便使它们成为研究层状组织、回路形成以及这些过程的中断如何与疾病相关的更好模型。
