Human cerebellar organoids with functional Purkinje cells.
Publication Year:
2024
PubMed ID:
38181749
Funding Grants:
Public Summary:
Studying human cerebellum development and disease has been difficult because existing models don’t fully replicate its complex cell types and functions. In this study, researchers created human cerebellar organoids (hCerOs) that mimic the fetal cerebellum, including a rare human-specific progenitor population never grown in the lab before. After two months, these organoids develop organized layers and form functional connections between different types of neurons, showing coordinated activity. With long-term culture, Purkinje cells—a critical type of cerebellar neuron—survive and mature, displaying properties similar to those in the human brain. This all-human model provides a powerful tool to study how different cerebellar cell types develop and how cerebellar diseases arise.
Scientific Abstract:
Research on human cerebellar development and disease has been hampered by the need for a human cell-based system that recapitulates the human cerebellum's cellular diversity and functional features. Here, we report a human organoid model (human cerebellar organoids [hCerOs]) capable of developing the complex cellular diversity of the fetal cerebellum, including a human-specific rhombic lip progenitor population that have never been generated in vitro prior to this study. 2-month-old hCerOs form distinct cytoarchitectural features, including laminar organized layering, and create functional connections between inhibitory and excitatory neurons that display coordinated network activity. Long-term culture of hCerOs allows healthy survival and maturation of Purkinje cells that display molecular and electrophysiological hallmarks of their in vivo counterparts, addressing a long-standing challenge in the field. This study therefore provides a physiologically relevant, all-human model system to elucidate the cell-type-specific mechanisms governing cerebellar development and disease.
