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

RM Marton, Y Miura, SA Sloan, Q Li, O Revah… - Nature …, 2019 - nature.com
Nature neuroscience, 2019nature.com
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 …
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.
nature.com