Researchers at the University of Southern California (USC) Stem Cell laboratory, led by Giorgia Quadrato, have successfully pioneered a groundbreaking human brain organoid model that can generate all major cell types of the cerebellum. The cerebellum, located in the hindbrain, plays a crucial role in movement, cognition, and emotion through its two main cell types: granule cells and Purkinje neurons.
For the first time, the scientists were able to grow Purkinje cells in an all-human system that possess the molecular and electrophysiological features of functional neurons. This extraordinary achievement in organoid-directed brain modeling has been documented in a scientific publication in the journal Cell Stem Cell.
The reproducible co-development and maturation of the main cell types of the cerebellum within the human organoid model opens up new avenues for exploring the underlying biology of cerebellar development and disorders, as well as advancing therapeutic interventions. Giorgia Quadrato, an assistant professor at the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at the Keck School of Medicine of USC, emphasizes the importance of this breakthrough.
The cerebellum not only controls movement but also plays significant roles in various cognitive functions, including language, spatial processing, working memory, executive functions, and emotional processing.
The degeneration of Purkinje cells is associated with several neurodevelopmental and neurodegenerative disorders, such as autism spectrum disorder and cerebellar ataxia, which affects muscle movement.
In addition to granule cells and Purkinje neurons, other neurons within the organoids, including excitatory and inhibitory neurons, formed functional circuits and exhibited coordinated network activity. This suggests that these neurons are also fully operational nerve cells.
Moreover, the organoids formed human-specific progenitor cells that are closely linked to medulloblastoma, the most common metastatic brain tumor in children. Consequently, the organoids can serve as a valuable model for studying this pediatric cancer and developing potential treatments.
Under specific external cues, the organoids were capable of developing anatomical features, such as layers, mirroring the normal embryonic brain development process.
The organoid model provides an unprecedented platform for discovering new treatments and therapies for a wide range of diseases.
According to Alexander Atamian, a Ph.D. candidate in the Quadrato Lab and the first author of the publication in Cell Stem Cell, this study has provided a physiologically relevant all-human model system that can elucidate the mechanisms specific to different cell types in cerebellar development and disease.
The study involved collaboration with researchers from USC, UCLA, the California Institute of Technology, and Spatial Genomics.
The groundbreaking organoid model developed by USC Stem Cell scientists holds immense potential in advancing our understanding of cerebellar development and associated disorders. It offers new avenues for research, which could ultimately lead to the development of innovative therapies and treatment options for various neurological conditions.
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