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Chunk #1 — Introduction

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Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes.
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been investigated before. Improved mechanistic understanding of the differentiation and maturation of human oligodendrocytes from OPCs is therefore of considerable interest as a point of potential therapeutic intervention. Specifically the excitable membrane properties of oligodendrocytes that are central to their physiological role have been shown in rodent studies to markedly change upon differentiation and maturation of the OPC to an oligodendrocyte. The necessity to explore oligodendrocyte maturation in a human context is underlined by evidence for both interspecies cellular and molecular differences in neurons and astrocytes 9, 10, 11, 12, 13 as well as specific differences in the spatial distribution and development of rodent and human oligodendrocytes 14. However, the conservation of excitable membrane properties throughout the maturation process in human oligodendrocytes remains unknown, despite their dysfunction being implicated in diseases such as ALS. The ability to derive oligodendrocyte lineage cells from human pluripotent stem cells (hPSCs) including from patients carrying disease causing mutations provides an opportunity to investigate the maturation and electrophysiological properties of human oligodendrocytes in both normal physiological and disease contexts 15, 16, 17.