Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures

Nat Neurosci. 2019 Mar;22(3):484-491. doi: 10.1038/s41593-018-0316-9. Epub 2019 Jan 28.

Abstract

Investigating human oligodendrogenesis and the interaction of oligodendrocytes with neurons and astrocytes would accelerate our understanding of the mechanisms underlying white matter disorders. However, this is challenging because of the limited accessibility of functional human brain tissue. Here, we developed a new differentiation method of human induced pluripotent stem cells to generate three-dimensional brain organoids that contain oligodendrocytes as well as neurons and astrocytes, called human oligodendrocyte spheroids. We found that oligodendrocyte lineage cells derived in human oligodendrocyte spheroids transitioned through developmental stages similar to primary human oligodendrocytes and that the migration of oligodendrocyte lineage cells and their susceptibility to lysolecithin exposure could be captured by live imaging. Moreover, their morphology changed as they matured over time in vitro and started myelinating neurons. We anticipate that this method can be used to study oligodendrocyte development, myelination, and interactions with other major cell types in the CNS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Astrocytes / physiology
  • Cell Culture Techniques / methods*
  • Cell Differentiation*
  • Cell Line
  • Cell Lineage
  • Humans
  • Induced Pluripotent Stem Cells / physiology
  • Neurons / physiology*
  • Oligodendroglia / metabolism
  • Oligodendroglia / physiology*
  • Spheroids, Cellular / physiology*
  • Transcriptome