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Induction of oligodendrocyte differentiation from adult human fibroblast-derived induced pluripotent stem cells

  • Shin-ichiro Ogawa
  • Yasuhito TokumotoEmail author
  • Jun Miyake
  • Teruyuki Nagamune
Report

Abstract

Induced pluripotent stem cells (iPSCs) prepared from somatic cells might become a novel therapeutic tool in regenerative medicine, especially for the central nervous system (CNS). In this study, we attempted to induce O4-positive (O4+) oligodendrocytes from adult human fibroblast-derived iPSCs in vitro. We used two adult human iPSC cell lines, 201B7 and 253G1. 201B7 was induced by four-gene transduction (oct4, sox2, klf4, c-myc), and 253G1 was induced by three-gene transduction (oct4, sox2, klf4). We treated these cells with two in vitro oligodendrocyte-directed differentiation protocols that were optimized for human embryonic stem cells. One protocol used platelet-derived growth factor as the major mitogen for oligodendrocyte lineage cells, and the other protocol used epidermal growth factor (EGF) as the mitogen. Although the differentiation efficiency was low (less than 0.01%), we could induce O4+ oligodendrocytes from 253G1 cells using the EGF-dependent differentiation protocol. This is the first report of the in vitro induction of oligodendrocytes differentiation from human iPSCs.

Keywords

Induced pluripotent stem cell Oligodendrocyte Myelin Human 

Notes

Acknowledgments

We extend special thanks to Shinya Yamanaka for making the human iPSCs, 201B7 and 253G1 available to us. We greatly appreciate Martin C. Raff for providing us with the mouse monoclonal O4 antibody. We thank Shinpei Tamaki for discussion and advice. This study was supported by a project grant from NEDO, Japan. Y.T. was partly supported by JST, ERATO, Suematsu Gas Biology project.

Supplementary material

11626_2011_9435_MOESM1_ESM.ppt (1.1 mb)
Supplemental Figure 1 O4+ oligodendrocyte derived from mouse iPSC. Mouse embryonic fibloblast-derived iPSCs were differentiated into oligodendrocyte in vitro as previously shown (Tokumoto et al. 2010). Cells were stained with an O4 antibody (green, right panel) and DAPI (blue, left panel). White arrows show the position of the O4+ cell. White scale bars mean 100 μm. (PPT 1131 kb)

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Copyright information

© The Society for In Vitro Biology 2011

Authors and Affiliations

  • Shin-ichiro Ogawa
    • 1
  • Yasuhito Tokumoto
    • 2
    • 3
    Email author
  • Jun Miyake
    • 2
  • Teruyuki Nagamune
    • 1
    • 2
  1. 1.Department of Chemistry and Biotechnology, Graduate School of EngineeringThe University of TokyoTokyoJapan
  2. 2.Department of Bioengineering, Graduate School of EngineeringThe University of TokyoTokyoJapan
  3. 3.Department of Biochemistry, School of MedicineKeio UniversityTokyoJapan

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