Generation and Characterization of Spiking and Nonspiking Oligodendroglial Progenitor Cells from Embryonic Stem Cells

Authors

  • Peng Jiang,

    1. Department of Biochemistry and Molecular Medicine, School of Medicine, Sacramento, California, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California, USA
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  • Chen Chen,

    1. Department of Biochemistry and Molecular Medicine, School of Medicine, Sacramento, California, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California, USA
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  • Xiao-Bo Liu,

    1. Center for Neuroscience, University of Texas Health Science Center at Houston, Houston, Texas, USA
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  • Vimal Selvaraj,

    1. Department of Biochemistry and Molecular Medicine, School of Medicine, Sacramento, California, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California, USA
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  • Wei Liu,

    1. Department of Biochemistry and Molecular Medicine, School of Medicine, Sacramento, California, USA
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  • Daniel H. Feldman,

    1. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California, USA
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  • Ying Liu,

    1. Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, Texas, USA
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  • David E. Pleasure,

    1. Department of Neurology, School of Medicine, University of California, Davis, California, USA
    2. Department of Pediatrics, School of Medicine, University of California, Davis, California, USA
    3. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California, USA
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  • Ronald A. Li,

    1. Department of Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China
    2. Department of Physiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China
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  • Wenbin Deng

    Corresponding author
    1. Department of Biochemistry and Molecular Medicine, School of Medicine, Sacramento, California, USA
    2. Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Sacramento, California, USA
    • Correspondence: Wenbin Deng, Ph.D., Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, 2425 Stockton Blvd., Sacramento, California 95817, USA. Telephone: 916-453-2287; Fax: 916-453-2288; e-mail: wbdeng@ucdavis.edu

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  • Author contributions: P.J.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing; C.C., collection and assembly of data and data analysis and interpretation; X.-B.L., V.S., W.L., and D.H.F.: collection and assembly of data; Y.L.: conception and design and provision of study material; D.E.P.: conception and design; R.A.L.: provision of study material; W.D.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.

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 GFP+/Olig2+ 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 α 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 myelin-deficient 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. Stem Cells 2013;31:2620–2631

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