Generation and characterization of spiking and nonspiking oligodendroglial progenitor cells from embryonic stem cells

Peng Jiang, Chen Chen, Xiao Bo Liu, Vimal Selvaraj, Wei Liu, Daniel H. Feldman, Ying Liu, David E. Pleasure, Ronald A. Li, Wenbin Deng

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Pluripotent stem cells (PSCs) have been differentiated into oligodendroglial progenitor cells (OPCs), providing promising cell replacement therapies for many central nervous system disorders. Studies from rodents have shown that brain OPCs express a variety of ion channels, and that a subset of brain OPCs express voltage-gated sodium channel (NaV), mediating the spiking properties of OPCs. However, it is unclear whether PSC-derived OPCs exhibit electrophysiological properties similar to brain OPCs and the role of NaV in the functional maturation of OPCs is unknown. Here, using a mouse embryonic stem cell (mESC) green fluorescent protein (GFP)-Olig2 knockin reporter line, we demonstrated that unlike brain OPCs, all the GFP1/Olig21 mESC-derived OPCs (mESC-OPCs) did not express functional NaV and failed to generate spikes (hence termed "nonspiking mESC-OPCs"), while expressing the delayed rectifier and inactivating potassium currents. By ectopically expressing NaV1.2 a subunit via viral transduction, we successfully generated mESC-OPCs with spiking properties (termed "spiking mESC-OPCs"). After transplantation into the spinal cord and brain of myelindeficient shiverer mice, the spiking mESC-OPCs demonstrated better capability in differentiating into myelin basic protein expressing oligodendrocytes and in myelinating axons in vivo than the nonspiking mESC-OPCs. Thus, by generating spiking and nonspiking mESC-OPCs, this study reveals a novel function of NaV in OPCs in their functional maturation and myelination, and sheds new light on ways to effectively develop PSC-derived OPCs for future clinical applications.

Original languageEnglish (US)
Pages (from-to)2620-2631
Number of pages12
JournalSTEM CELLS
Volume31
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Action potential
  • Embryonic stem cell
  • Myelination
  • Oligodendroglial progenitor cell
  • Voltage-gated ion channel

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Jiang, P., Chen, C., Liu, X. B., Selvaraj, V., Liu, W., Feldman, D. H., Liu, Y., Pleasure, D. E., Li, R. A., & Deng, W. (2013). Generation and characterization of spiking and nonspiking oligodendroglial progenitor cells from embryonic stem cells. STEM CELLS, 31(12), 2620-2631. https://doi.org/10.1002/stem.1515