Skip to main content
SpringerLink
Log in

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

  • Report
  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.

Similar content being viewed by others

References

  • Billon N.; Jolicoeur C.; Ying Q. L.; Smith A.; Raff M. Normal timing of oligodendrocyte development from genetically engineered, lineage-selectable mouse ES cells. J Cell Sci 115: 3657–3665; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Eisenbrath G. S.; Walsh F. S.; Nirenberg M. Monoclonal antibody to plasma membrane antigen of neurons. Proc Natl Acad Sci USA 76: 4913–4917; 1979.

    Article  Google Scholar 

  • Franklin R. J.; Ffrench-Constant C. Remyelination in the CNS: From biology to therapy Nature Rev Neurosci 9: 839–855; 2008.

    Article  CAS  Google Scholar 

  • Hu B.; Du Z.; Zang S. Differentiation of human oligodendrocytes from pluripotent stem cells. Nature Protocols 4: 1614–1622; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Kang S. M.; Cho M. S.; Seo H.; Yoon C. J.; Oh S. K.; Choi Y. M.; Kim D. W. Efficient induction of oligodendrocytes from human embryonic stem cells. Stem Cells 25: 419–424; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Miura K.; Okada Y.; Aoi T.; Okada A.; Takahashi K.; Okita K.; Nakagawa M.; Koyanagi M.; Tanabe K.; Ohnuki M.; Ogawa D.; Ikeda E.; Okano H.; Yamanaka S. Variation in the safety of induced pluripotent stem cell lines. Nature Biotech 27: 743–745; 2009.

    Article  CAS  Google Scholar 

  • Nakagawa M.; Koyanagi M.; Tanabe K.; Takahashi K.; Ichisaka T.; Aoi T.; Okita K.; Mochiduki Y.; Takizawa N.; Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblast. Nature Biotech 26: 101–106; 2008.

    Article  CAS  Google Scholar 

  • Nistor G. I.; Totoiu M. O.; Haque N.; Carpenter M. K.; Keirstead H. S. Human embryonic stem cells differentiated into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49: 385–396; 2005.

    Article  PubMed  Google Scholar 

  • Noble M.; Murray K.; Stroobant P.; Waterfield M. D.; Riddle P. Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333: 560–562; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Ogawa S.; Tokumoto Y.; Miyake J.; Nagamune T. Immunopanning selection of A2B5- positive cells increased the differentiation efficiency of induced pluripotent stem cells into oligodendrocytes. Neurosci Letters 489: 79–83; 2011.

    Article  CAS  Google Scholar 

  • Okita K.; Ichisaka T.; Yamanaka S.; Generation of germline-competent induced pluripotent stem cells. Nature 448: 313–317; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Onorati M.; Camnasio S.; Binetti M.; Jung C. B.; Moretti A.; Cattaneo E. Neuropotent self-renewing neural stem (NS) cells derived from mouse induced pluripotent stem (iPS) cells. Mol Cell Neurosci 43: 287–295; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Pfeiffer S. E.; Warrington A. E.; Bansal R. The oligodendrocyte and its many cellular processes. Trends Cell Biol 3: 191–197; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Raff M. C.; Lillien L. E.; Richardson W. D.; Burne J. F.; Noble M. D. Platelet-derived growth factor from astrocytes drives the clock that times oligodendrocyte development in culture. Nature 333: 562–565; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Sher F.; Balasubramaniyan V.; Boddeke E.; Copray S. Oligodendrocyte differentiation and implantation: New insights for remyelinating cell therapy. Curr Opin Neurol 21: 607–614; 2008.

    Article  PubMed  Google Scholar 

  • Sommer I.; Schachner M. Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: An immunocytological study in the central nerve system. Dev Biol 83: 311–327; 1981.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K.; Tanabe K.; Ohnuki M.; Narita M.; Ichisaka T.; Tomoda K.; Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131: 861–872; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi K.; Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663–676; 2006.

    Google Scholar 

  • Tokumoto Y.; Ogawa S.; Nagamune T.; Miyake J. Comparison of efficiency of terminal differentiation of oligodendrocytes from induced pulipotent stem cells versus embryonic stem cells in vitro. J Biosci Bioeng 109: 622–628; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji O.; Miura K.; Okada Y.; Fujiyoshi K.; Mukaino M.; Nagoshi N.; Kitamura K.; Kumagai G.; Nishino M.; Tomisato S.; Higashi H.; Nagai T.; Katoh H.; Kohda K.; Matsuzaki Y.; Yuzaki M.; Ikeda E.; Toyama Y.; Nakamura M.; Yamanaka S.; Okano H. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci USA 107: 12704–12709; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Wernig M.; Meissner A,; Foreman R.; Brambrink T.; Ku M.; Hochedlinger K.; Bernstein B. E.; Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448: 318–324; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Wernig M.; Zhao J. –P.; Pruszak J. J.; Hedlund E.; Fu D.; Soldner F.; Broccoli V.; Constantine-Paton M.; Isacson O.; Jaenisch R. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci USA 105: 5856–5861; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Yamanaka Y. A fresh look at iPS cells. Cell 137: 13–17; 2009

    Article  PubMed  CAS  Google Scholar 

  • Zao XX.; Li W.; Lv Z.; Liu L.; Tong M.; Hai T.; Hao J.; Guo C.; Ma Q.; Wang L.; Zeng F.; Zhou Q. iPS cells produce viable mice through tetraploid complementation. Nature 461: 86–90; 2009.

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Author notes

  1. Yasuhito Tokumoto

    Present address: Department of Biochemistry, School of Medicine, Keio University, Shinanomachi 35, Shinjyuku-ku, Tokyo, 160–8582, Japan

Authors and Affiliations

  1. Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113–8656, Japan

    Shin-ichiro Ogawa & Teruyuki Nagamune

  2. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113–8656, Japan

    Yasuhito Tokumoto, Jun Miyake & Teruyuki Nagamune

Authors
  1. Shin-ichiro Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuhito Tokumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun Miyake
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teruyuki Nagamune
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhito Tokumoto.

Additional information

Editor: T. Okamoto

Electronic supplementary material

Below is the link to the electronic supplementary material.

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogawa, Si., Tokumoto, Y., Miyake, J. et al. Induction of oligodendrocyte differentiation from adult human fibroblast-derived induced pluripotent stem cells. In Vitro Cell.Dev.Biol.-Animal 47, 464–469 (2011). https://doi.org/10.1007/s11626-011-9435-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-011-9435-2

Keywords

Search

Navigation