期刊
STEM CELLS
卷 31, 期 12, 页码 2620-2631出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.1515
关键词
Embryonic stem cell; Oligodendroglial progenitor cell; Voltage-gated ion channel; Action potential; Myelination
资金
- National Institutes of Health [R01NS061983, R01ES015988]
- National Multiple Sclerosis Society
- Shriners Hospitals for Children
- California Institute for Regenerative Medicine
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 (Na-V), 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 Na-V 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 Na-V and failed to generate spikes (hence termed nonspiking mESC-OPCs), while expressing the delayed rectifier and inactivating potassium currents. By ectopically expressing Na(V)1.2 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 Na-V in OPCs in their functional maturation and myelination, and sheds new light on ways to effectively develop PSC-derived OPCs for future clinical applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据