Induction of myelinating oligodendrocytes in human cortical spheroids

Cerebral organoids provide an accessible system for investigations of cellular composition, interactions, and organization but have lacked oligodendrocytes, the myelinating glia of the central nervous system. Here we reproducibly generated oligodendrocytes and myelin in ‘oligocortical spheroids’ der...

Full description

Saved in:
Bibliographic Details
Published inNature methods Vol. 15; no. 9; pp. 700 - 706
Main Authors Madhavan, Mayur, Nevin, Zachary S., Shick, H. Elizabeth, Garrison, Eric, Clarkson-Paredes, Cheryl, Karl, Molly, Clayton, Benjamin L. L., Factor, Daniel C., Allan, Kevin C., Barbar, Lilianne, Jain, Tanya, Douvaras, Panagiotis, Fossati, Valentina, Miller, Robert H., Tesar, Paul J.
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.09.2018
Nature Publishing Group
Subjects
631/136/142
631/136/532
631/378/2596
631/532/2064
Animals
Bioinformatics
Biological Microscopy
Biological Techniques
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Brain
Brain research
Cell culture
Cell Differentiation
Central nervous system
Cerebral Cortex - cytology
Cortex
Genetic research
Glia
Humans
Life Sciences
Myelin
Myelin sheath
Myelin Sheath - metabolism
Myelination
Nervous system
Oligodendrocytes
Oligodendroglia - cytology
Oligodendroglia - metabolism
Organoids
Phenotypes
Pluripotency
Pluripotent Stem Cells - cytology
Proteomics
Spheroids
Spheroids, Cellular - cytology
Spheroids, Cellular - metabolism
Stem cell research
Stem cells
Online AccessGet full text

Cover

More Information
Summary:Cerebral organoids provide an accessible system for investigations of cellular composition, interactions, and organization but have lacked oligodendrocytes, the myelinating glia of the central nervous system. Here we reproducibly generated oligodendrocytes and myelin in ‘oligocortical spheroids’ derived from human pluripotent stem cells. Molecular features consistent with those of maturing oligodendrocytes and early myelin appeared by week 20 in culture, with further maturation and myelin compaction evident by week 30. Promyelinating drugs enhanced the rate and extent of oligodendrocyte generation and myelination, and spheroids generated from human subjects with a genetic myelin disorder recapitulated human disease phenotypes. Oligocortical spheroids provide a versatile platform for studies of myelination of the developing central nervous system and offer new opportunities for disease modeling and therapeutic development. A method for generating cortical spheroids from human pluripotent stem cells produces maturing oligodendrocytes that can myelinate axons and model myelin disease and drug effects.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors contributed equally to this work
Author Contributions
M.M., Z.S.N. and P.J.T. conceived and initiated the project. M.M. and Z.S.N. developed the oligocortical spheroid protocol and generated spheroids for all experiments. M.M., H.E.S. B.L.L.C., K.C.A. and L.B. performed immunohistochemistry and quantification and generated associated figures. D.C.F. and B.L.L.C. analyzed RNAseq data and generated associated figures. E.G., C.C-P., and R.H.M. designed and performed electron microscopy experiments and analysis and generated associated figures. H.E.S. maintained pluripotent stem cell lines. T.J., P.D., and V.F. independently replicated the oligocortical spheroid protocol. Z.S.N., M.M., and P.J.T. wrote the manuscript with input from all authors.
ISSN:1548-7091
1548-7105
1548-7105
DOI:10.1038/s41592-018-0081-4