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Induction of myelinating oligodendrocytes in human cortical spheroids

by Miller, Robert H , Fossati, Valentina , Clarkson-Paredes, Cheryl , Jain, Tanya , Shick, H Elizabeth , Allan, Kevin C , Douvaras, Panagiotis , Factor, Daniel C , Nevin, Zachary S , Clayton, Benjamin L L , Tesar, Paul J , Barbar, Lilianne , Karl, Molly , Garrison, Eric , Madhavan, Mayur

in Cell culture / Central nervous system / Cortex / Myelin / Myelination / Nervous system / Oligodendrocytes / Organoids / Phenotypes / Pluripotency / Spheroids / Stem cells

2018

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Induction of myelinating oligodendrocytes in human cortical spheroids

in Cell culture / Central nervous system / Cortex / Myelin / Myelination / Nervous system / Oligodendrocytes / Organoids / Phenotypes / Pluripotency / Spheroids / Stem cells

2018

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Induction of myelinating oligodendrocytes in human cortical spheroids

in Cell culture / Central nervous system / Cortex / Myelin / Myelination / Nervous system / Oligodendrocytes / Organoids / Phenotypes / Pluripotency / Spheroids / Stem cells

2018

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Journal Article

Induction of myelinating oligodendrocytes in human cortical spheroids

Miller, Robert H,

Fossati, Valentina,

Clarkson-Paredes, Cheryl,

Jain, Tanya,

Shick, H Elizabeth,

Allan, Kevin C,

Douvaras, Panagiotis,

Factor, Daniel C,

Nevin, Zachary S,

Clayton, Benjamin L L,

Tesar, Paul J,

Barbar, Lilianne,

Karl, Molly,

Garrison, Eric,

Madhavan, Mayur

2018

Overview

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.

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Publisher

Nature Publishing Group

Subject

Cell culture

/ Central nervous system

/ Cortex

/ Myelin

/ Myelination

/ Nervous system

/ Oligodendrocytes