TitleiPSC-derived myelinoids to study myelin biology of humans.
Publication TypeJournal Article
Year of Publication2021
AuthorsJames OG, Selvaraj BT, Magnani D, Burr K, Connick P, Barton SK, Vasistha NA, Hampton DW, Story D, Smigiel R, Ploski R, Brophy PJ, Ffrench-Constant C, Lyons DA, Chandran S
JournalDev Cell
Date Published2021 May 03
KeywordsAxons, Humans, Induced Pluripotent Stem Cells, Myelin Sheath, Nerve Growth Factors, Organoids, Tetanus Toxin, Time Factors

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.

Alternate JournalDev Cell
PubMed ID33945785
PubMed Central IDPMC8098746
Grant List214244/Z/18/Z / WT_ / Wellcome Trust / United Kingdom
107008 / WT_ / Wellcome Trust / United Kingdom
G0601744 / MRC_ / Medical Research Council / United Kingdom
MR/P006272/1 / MRC_ / Medical Research Council / United Kingdom
/ WT_ / Wellcome Trust / United Kingdom
MR/N013255/1 / MRC_ / Medical Research Council / United Kingdom
MR/L023784/2 / MRC_ / Medical Research Council / United Kingdom
102836/Z/13/Z / WT_ / Wellcome Trust / United Kingdom