Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes

Stem Cells
Matthew R LiveseySiddharthan Chandran

Abstract

Rodent-based studies have shown that the membrane properties of oligodendrocytes play prominent roles in their physiology and shift markedly during their maturation from the oligodendrocyte precursor cell (OPC) stage. However, the conservation of these properties and maturation processes in human oligodendrocytes remains unknown, despite their dysfunction being implicated in human neurodegenerative diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Here, we have defined the membrane properties of human oligodendrocytes derived from pluripotent stem cells as they mature from the OPC stage, and have identified strong conservation of maturation-specific physiological characteristics reported in rodent systems. We find that as human oligodendrocytes develop and express maturation markers, they exhibit a progressive decrease in voltage-gated sodium and potassium channels and a loss of tetrodotoxin-sensitive spiking activity. Concomitant with this is an increase in inwardly rectifying potassium channel activity, as well as a characteristic switch in AMPA receptor composition. All these steps mirror the developmental trajectory observed in rodent systems. Oligodendrocytes derived from mutant C9ORF72-carr...Continue Reading

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Citations

Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Laura FerraiuoloBrian K Kaspar
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Methods Mentioned

BETA
mechanical dissociation
PCR
Fluorescence
Flow

Software Mentioned

ImageJ64
WinEDR

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