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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 |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 20 Jul 2022 11:30 |
| Last Modified: | 22 Oct 2022 18:37 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/86723 |
| DOI: | 10.1016/j.devcel.2021.04.006 |
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