Abstract
The development of the human brain is a complex multi-stage process including the formation of various types of neural cells and their interactions. Many fundamental mechanisms of neurogenesis have been established due to the studying of model animals. However, significant differences in the brain structure compared to other animals do not allow considering all aspects of the human brain formation, which could play the main role in the development of unique cognitive abilities for human. Four years ago, Lancaster’s group elaborated human pluripotent stem cell-derived three-dimensional cerebral organoid technology, which opened a unique opportunity for researchers to model early stages of human neurogenesis in vitro. Cerebral organoids closely remodel many endogenous brain regions with specific cell composition like ventricular zone with radial glia, choroid plexus, and cortical plate with upper and deeper-layer neurons. Moreover, human brain development includes interactions between different brain regions. Generation of hybrid three-dimensional cerebral organoids with different brain region identity allows remodeling some of them, including long-distance neuronal migration or formation of major axonal tracts. In this review, we consider the technology of obtaining human pluripotent stem cell-derived three-dimensional cerebral organoids with different modifications and with different brain region identity. In addition, we discuss successful implementation of this technology in fundamental and applied research like modeling of different neurodevelopmental disorders and drug screening. Finally, we regard existing problems and prospects for development of human pluripotent stem cell-derived threedimensional cerebral organoid technology.
Highlights
The development of the human brain is a complex multi-stage process including the formation of various types of neural cells and their interactions
Significant differences in the brain structure compared to other animals do not allow considering all aspects of the human brain formation, which could play the main role in the development of unique cognitive abilities for human
Lancaster’s group elaborated human pluripotent stem cell-derived three-dimensional cerebral organoid technology, which opened a unique opportunity for researchers to model early stages of human neurogenesis in vitro
Summary
Развитие головного мозга человека представляет собой сложный многоэтапный процесс, включающий образование различных типов нейральных клеток и их взаимодействия. Однако значительные структурные различия головного мозга по сравнению с другими животными не позволяют рассмотреть все аспекты формирования головного мозга у человека, которые могут играть решающую роль для развития его уникальных когнитивных способностей. Технология ЦО предоставляет абсолютно уникальную возможность воссоздавать начальные этапы развития головного мозга человека и исследовать поведение нервных клеток в условиях, максимально приближенных к in vivo. Ранние этапы развития головного мозга человека in vivo Человеческий мозг содержит десятки миллионов различных нейронов и глиальных клеток, которые путем сложных взаимодействий обеспечивают его уникальные функции. Процесс раннего нейрогенеза заканчивается тем, что все типы нейральных предшественников делятся симметрично и дают начало нейронам, которые мигрируют в сторону базальной мембраны, используя для своего движения отростки радиальной глии.
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