Induction of myelinating oligodendrocytes in human cortical spheroids

被引：252

作者：

Madhavan, Mayur ^{[1
]}

Nevin, Zachary S. ^{[1
]}

Shick, H. Elizabeth ^{[1
]}

Garrison, Eric ^{[2
]}

Clarkson-Paredes, Cheryl ^{[3
]}

Karl, Molly ^{[2
]}

Clayton, Benjamin L. L. ^{[1
]}

Factor, Daniel C. ^{[1
]}

Allan, Kevin C. ^{[1
]}

Barbar, Lilianne ^{[1
]}

Jain, Tanya ^{[4
]}

Douvaras, Panagiotis ^{[4
]}

Fossati, Valentina ^{[4
]}

Miller, Robert H. ^{[2
]}

Tesar, Paul J. ^{[1
]}

机构：

[1] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH 44106 USA

[2] George Washington Univ, Sch Med & Hlth Sci, Dept Anat & Regenerat Biol, Washington, DC 20052 USA

[3] George Washington Univ, Sch Med & Hlth Sci, Nanofabricat & Imaging Ctr, Washington, DC 20052 USA

[4] New York Stem Cell Fdn, Res Inst, New York, NY USA

来源：

NATURE METHODS | 2018年 / 15卷 / 09期

关键词：

PLURIPOTENT STEM-CELLS; PELIZAEUS-MERZBACHER-DISEASE; HUMAN BRAIN-DEVELOPMENT; CENTRAL-NERVOUS-SYSTEM; CEREBRAL ORGANOIDS; MULTIPLE-SCLEROSIS; GROWTH-FACTOR; CLEMASTINE FUMARATE; SELF-ORGANIZATION; PROGENITOR CELLS;

D O I：

10.1038/s41592-018-0081-4

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：700 / +

页数：9

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