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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\u2019s 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.<\/jats:p>","DOI":"10.1038\/s42003-026-10180-5","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T23:35:28Z","timestamp":1778196928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modeling Friedreich\u2019s ataxia with Bergmann glia-enriched human cerebellar organoids"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8461-5878","authenticated-orcid":false,"given":"Seungmi","family":"Ryu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8544-3286","authenticated-orcid":false,"given":"Jason","family":"Inman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyenjong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0226-1998","authenticated-orcid":false,"given":"Vukasin M.","family":"Jovanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeliz","family":"Gedik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogita","family":"Jethmalani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inae","family":"Hur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majid","family":"Harouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty","family":"Voss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Lack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-2085","authenticated-orcid":false,"given":"Jack","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Ormanoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4523-9977","authenticated-orcid":false,"given":"Anton","family":"Simeonov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-6215","authenticated-orcid":false,"given":"Carlos A.","family":"Tristan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3941-1838","authenticated-orcid":false,"given":"Ilyas","family":"Singe\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"10180_CR1","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s41586-023-06884-x","volume":"625","author":"M Sepp","year":"2024","unstructured":"Sepp, M. et al. 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