iPSC-derived myelinoids to study myelin biology of humans

• DOI: 10.1016/j.devcel.2021.04.006
• Publication Date: 2021-05-03T15:11:45Z
• Authors: Owen G. James; Bhuvaneish T. Sel...; Dario Magnani; Karen Burr; Peter Connick; Samantha K. Barton; Navneet A. Vasistha; David W. Hampton; David Story; Robert Smigiel; Rafal Ploski; Peter J. Brophy; Charles ffrench-C...; David A. Lyons; Siddharthan Chandran
• Keywords: Organoids; 570; Technology; Time Factors; Tetanus Toxin; Induced Pluripotent Stem Cells; 610; Correction; Humans; Nerve Growth Factors; Axons; Myelin Sheath; 3. Good health

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