TY - JOUR
KW - Developmental neurogenesis
KW - disease model
KW - Neural Stem Cells
KW - Stem-cell differentiation
AU - Seungmi Ryu
AU - Jason Inman
AU - Hyenjong Hong
AU - Vukasin M. Jovanovic
AU - Qiang Chen
AU - Yeliz Gedik
AU - Yogita Jethmalani
AU - Inae Hur
AU - Majid Harouni
AU - Ty Voss
AU - Justin Lack
AU - Jack Collins
AU - Pinar Ormanoglu
AU - Anton Simeonov
AU - Carlos A. Tristan
AU - Ilyas Singec
AB - The human cerebellum is implicated in various neurological and psychiatric diseases, but its complex development and cellular diversity have posed challenges for in vitro modeling. Here, we report the generation of human induced pluripotent stem cell (iPSC)-derived cerebellar organoids (hCBOs) that are characterized by induction of rhombomere 1 (R1) cellular identity and followed by derivation of typical neuronal and glial cell types of the cerebellum. In contrast to forebrain organoids with multiple neural rosettes and inside-out neuronal migration, hCBOs develop a germinal zone on the outermost surface of the organoids with outside-in neuronal migration. These hCBOs produce various neuronal cell types resembling granule neurons, Purkinje cells, Golgi neurons, and deep cerebellar nuclei. By using a glial induction strategy, we generate Bergmann glial cells (BGCs) that serve as scaffolds for migratory granule cells and enhance electrophysiological activity of the hCBOs. Furthermore, by generating hCBOs from patients with Friedreich’s ataxia (FRDA), we reveal disease-specific phenotypes that can be reversed by histone deacetylase (HDAC) inhibitors and gene editing by CRISPR-Cas9. Taken together, our advanced hCBO model provides new opportunities to investigate the mechanisms of cerebellar ontogenesis and utilize patient-derived iPSCs for translational research.
BT - Communications Biology
DA - 2026-05-08
DO - 10.1038/s42003-026-10180-5
LA - en
N2 - The human cerebellum is implicated in various neurological and psychiatric diseases, but its complex development and cellular diversity have posed challenges for in vitro modeling. Here, we report the generation of human induced pluripotent stem cell (iPSC)-derived cerebellar organoids (hCBOs) that are characterized by induction of rhombomere 1 (R1) cellular identity and followed by derivation of typical neuronal and glial cell types of the cerebellum. In contrast to forebrain organoids with multiple neural rosettes and inside-out neuronal migration, hCBOs develop a germinal zone on the outermost surface of the organoids with outside-in neuronal migration. These hCBOs produce various neuronal cell types resembling granule neurons, Purkinje cells, Golgi neurons, and deep cerebellar nuclei. By using a glial induction strategy, we generate Bergmann glial cells (BGCs) that serve as scaffolds for migratory granule cells and enhance electrophysiological activity of the hCBOs. Furthermore, by generating hCBOs from patients with Friedreich’s ataxia (FRDA), we reveal disease-specific phenotypes that can be reversed by histone deacetylase (HDAC) inhibitors and gene editing by CRISPR-Cas9. Taken together, our advanced hCBO model provides new opportunities to investigate the mechanisms of cerebellar ontogenesis and utilize patient-derived iPSCs for translational research.
PY - 2026
T2 - Communications Biology
TI - Modeling Friedreich’s ataxia with Bergmann glia-enriched human cerebellar organoids
UR - https://www.nature.com/articles/s42003-026-10180-5
Y2 - 2026-05-21
SN - 2399-3642
ER -