iPSC-derived myelinoids to study myelin biology of humans

James, Owen G., Selvaraj, Bhuvaneish T., Magnani, Dario, Burr, Karen, Connick, Peter, Barton, Samantha K., Vasistha, Navneet A., Hampton, David W., Story, David, Smigiel, Robert, Ploski, Rafal, Brophy, Peter J., ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377, Lyons, David A. and Chandran, Siddharthan (2021) iPSC-derived myelinoids to study myelin biology of humans. Developmental Cell, 56 (9). 1346-1358.e6. ISSN 1534-5807

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Abstract

Myelination is essential for central nervous system (CNS) formation, health, and function. Emerging evidence of oligodendrocyte heterogeneity in health and disease and divergent CNS gene expression profiles between mice and humans supports the development of experimentally tractable human myelination systems. Here, we developed human iPSC-derived myelinating organoids (“myelinoids”) and quantitative tools to study myelination from oligodendrogenesis through to compact myelin formation and myelinated axon organization. Using patient-derived cells, we modeled a monogenetic disease of myelinated axons (Nfasc155 deficiency), recapitulating impaired paranodal axo-glial junction formation. We also validated the use of myelinoids for pharmacological assessment of myelination—both at the level of individual oligodendrocytes and globally across whole myelinoids—and demonstrated reduced myelination in response to suppressed synaptic vesicle release. Our study provides a platform to investigate human myelin development, disease, and adaptive myelination.

Item Type: Article
Additional Information: Erratum: https://doi.org/10.1016/j.devcel.2021.12.009
Uncontrolled Keywords: adaptive myelination,disease modelling,human myelination,human stem cell,ipsc,myelin,myelinoid,oligodendrocyte,organoid,paranode,molecular biology,biochemistry, genetics and molecular biology(all),developmental biology,cell biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 20 Jul 2022 11:30
Last Modified: 12 Aug 2022 05:37
URI: https://ueaeprints.uea.ac.uk/id/eprint/86723
DOI: 10.1016/j.devcel.2021.04.006

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