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iPSC-derived myelinoids to study myelin biology of humans
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 myelinatio...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098746/ https://www.ncbi.nlm.nih.gov/pubmed/33945785 http://dx.doi.org/10.1016/j.devcel.2021.04.006 |
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author | 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 Lyons, David A. Chandran, Siddharthan |
author_facet | 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 Lyons, David A. Chandran, Siddharthan |
author_sort | James, Owen G. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8098746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80987462021-05-13 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 Lyons, David A. Chandran, Siddharthan Dev Cell Technology 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. Cell Press 2021-05-03 /pmc/articles/PMC8098746/ /pubmed/33945785 http://dx.doi.org/10.1016/j.devcel.2021.04.006 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Technology 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 Lyons, David A. Chandran, Siddharthan iPSC-derived myelinoids to study myelin biology of humans |
title | iPSC-derived myelinoids to study myelin biology of humans |
title_full | iPSC-derived myelinoids to study myelin biology of humans |
title_fullStr | iPSC-derived myelinoids to study myelin biology of humans |
title_full_unstemmed | iPSC-derived myelinoids to study myelin biology of humans |
title_short | iPSC-derived myelinoids to study myelin biology of humans |
title_sort | ipsc-derived myelinoids to study myelin biology of humans |
topic | Technology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098746/ https://www.ncbi.nlm.nih.gov/pubmed/33945785 http://dx.doi.org/10.1016/j.devcel.2021.04.006 |
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