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Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2019-01-28 , DOI: 10.1038/s41593-018-0316-9
Rebecca M Marton 1, 2 , Yuki Miura 1 , Steven A Sloan 1 , Qingyun Li 3 , Omer Revah 1 , Rebecca J Levy 4 , John R Huguenard 4 , Sergiu P Pașca 1, 5
Affiliation  

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.

中文翻译:

人三维神经培养中少突胶质细胞的分化和成熟。

研究人类少突胶质细胞生成以及少突胶质细胞与神经元和星形胶质细胞的相互作用将加速我们对白质疾病潜在机制的理解。然而,由于功能性人脑组织的可及性有限,这具有挑战性。在这里,我们开发了一种新的人类诱导多能干细胞分化方法,以生成包含少突胶质细胞以及神经元和星形胶质细胞的三维脑类器官,称为人类少突胶质细胞球体。我们发现源自人类少突胶质细胞球体的少突胶质细胞谱系细胞通过类似于原代人类少突胶质细胞的发育阶段转变,并且可以通过实时成像捕获少突胶质细胞谱系细胞的迁移及其对溶血卵磷脂暴露的易感性。而且,随着它们在体外随着时间的推移成熟并开始形成髓鞘神经元,它们的形态发生了变化。我们预计该方法可用于研究少突胶质细胞的发育、髓鞘形成以及与 CNS 中其他主要细胞类型的相互作用。
更新日期:2019-01-29
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