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Variation in Hematopoietic Potential of Induced Pluripotent Stem Cell Lines

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Abstract

Induced pluripotent stem (iPS) cells were originally generated from somatic cells by ectopic expression of four transcription factor genes: Oct3/4, Sox2, Klf4 and c-Myc. Currently, iPS cell lines differ in tissue origin, the combination of factors used to construct them, the method of gene delivery and expression of pluripotency markers. Thus to evaluate iPS cells for haematotherapy, the hematopoietic potential among iPS lines should be compared. Here, we compare differentiation capacity of six iPS lines into mesodermal cells and hematopoietic cells (HCs) through embryoid body (EB) formation. We show that the mouse embryonic fibroblast (MEF)-derived iPS lines 20D17 and 178B5 resemble CCE ES cells in terms of morphology in culture, number and size of EBs and differentiation capacity into mesodermal cells compared to iPS cells derived from adults, although all iPS lines could form EBs. The number of mesodermal cells differentiated from MEF-derived iPS cell lines showed a 3.9–407-fold increase compared to that from iPS lines derived from adults. Furthermore, 178B5 iPS cells generated Ter119+ erythroid cells (3.35%) efficiently in culture. We conclude that hematopoietic potential differs among the six lines and that MEF-derived 20D17 and 178B5 iPS cells generate HCs more efficiently than adult–derived iPS cells.

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References

  1. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–675.

    Article  PubMed  CAS  Google Scholar 

  2. Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germ-line competent induced pluripotent stem cells. Nature, 448, 313–317.

    Article  PubMed  CAS  Google Scholar 

  3. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., et al. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol, 26, 101–106.

    Article  PubMed  CAS  Google Scholar 

  4. Stadtfeld, M., Brennand, K., & Hochedlinger, K. (2008). Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol, 18, 890–894.

    Article  PubMed  CAS  Google Scholar 

  5. Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., & Yamanaka, S. (2008). Generation of mouse induced pluripotent stem cells without viral vectors. Science, 322, 949–953.

    Article  PubMed  CAS  Google Scholar 

  6. Aoi, T., Yae, K., Nakagawa, M., Ichisaka, T., Okita, K., Takahashi, K., et al. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science, 321, 699–702.

    Article  PubMed  CAS  Google Scholar 

  7. Hanna, J., Markoulaki, S., Schorderet, P., et al. (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell, 133, 250–264.

    Article  PubMed  CAS  Google Scholar 

  8. Ye, Z., Zhan, H., Mali, P., Dowey, S., Williams, D. M., Jang, Y. Y., et al. (2009). Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood, 114, 5473–5480.

    Article  PubMed  CAS  Google Scholar 

  9. Takenaka, C., Nishishita, N., Takada, N., Jakt, L. M., & Kawamata, S. (2010). Effective generation of iPS cells from CD34+ cord blood cells by inhibition of p53. Exp Hematol, 38, 154–162.

    Article  PubMed  CAS  Google Scholar 

  10. Lengerke, C., Grauer, M., Niebuhr, N. I., Riedt, T., Kanz, L., Park, I. H., et al. (2009). Hematopoietic development from human induced pluripotent stem cells. Ann NY Acad Sci, 1176, 219–227.

    Article  PubMed  CAS  Google Scholar 

  11. Doetschman, T. C., Eistetter, H., Katz, M., Schmidt, W., & Kemler, R. (1985). The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J Embryol Exp Morphol, 87, 27–45.

    PubMed  CAS  Google Scholar 

  12. Wiles, M. V., & Keller, G. (1991). Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development, 111, 259–267.

    PubMed  CAS  Google Scholar 

  13. Keller, G., Kennedy, M., Papayannopoulou, T., & Wiles, M. V. (1993). Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol, 13, 473–486.

    PubMed  CAS  Google Scholar 

  14. Nakano, T., Kodama, H., & Honjo, T. (1994). Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science, 265, 1098–1101.

    Article  PubMed  CAS  Google Scholar 

  15. Nakano, T., Kodama, H., & Honjo, T. (1996). In vitro development of primitive and definitive erythrocytes from different precursors. Science, 272, 722–724.

    Article  PubMed  CAS  Google Scholar 

  16. Nishigawa, S. I., Nishigawa, S., Hirashima, M., Matsuyoshi, N., & Kodama, H. (1998). Progressive lineage analysis by cell sorting and culture identifies FLK1+ VE-caherin+ cells at a diverging point of endothelial and hemopoietic lineage. Development, 125, 1747–1757.

    Google Scholar 

  17. Flamme, I., Breier, G., & Risau, W. (1995). Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo. Dev Biol, 169, 699–712.

    Article  PubMed  CAS  Google Scholar 

  18. Huber, T. L., Kouskoff, V., Fehling, H. J., Palis, J., & Keller, G. (2004). Haemangioblast commitment is initiated in the primitive streak of the mouse embryo. Nature, 432, 625–630.

    Article  PubMed  CAS  Google Scholar 

  19. Choi, K., Kennedy, M., Kazarov, A., Papadimitriou, J. C., & Keller, G. (1998). A common precursor for hematopoietic and endothelial cells. Development, 125, 725–732.

    PubMed  CAS  Google Scholar 

  20. Fehling, H. J., Lacaud, G., Kubo, A., Kennedy, M., Robertson, S., Keller, G., et al. (2003). Tracking mesoderm induction and its specification to the hemangioblast during embryonic stem cell differentiation. Development, 130, 4217–4227.

    Article  PubMed  CAS  Google Scholar 

  21. Miura, K., Okeda, Y., Aoi, T., et al. (2009). Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol, 27, 743–745.

    Article  PubMed  CAS  Google Scholar 

  22. Hadjantonakis, A. K., Macmaster, S., & Nagy, A. (2002). Embryonic stem cells and mice expressing different GFP variants for multiple non-invasive reporter usage within a single animal. BMC Biotechnol, 2, 11.

    Article  PubMed  Google Scholar 

  23. Hanna, J., Wernig, M., Markoulaki, S., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318, 1920–1923.

    Article  PubMed  CAS  Google Scholar 

  24. Park, I. H., Arora, N., Huo, H., et al. (2008). Disease-specific induced pluripotent stem cells. Cell, 134, 877–886.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This research was partially supported by the Ministry of Education, Science, Sports and Culture. Dr. Kulkeaw Kasem was supported by a scholarship from the Ajinomoto Foundation. We thank Dr. Keisuke Okita, Ms. Tomoko Yokoo, and Mr. Tatsuya Sasaki for technical support. All iPS cell lines were kindly provided by Dr. Shinya Yamanaka.

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All disclosures will be published if the manuscript is accepted.

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Authors and Affiliations

  1. Department of Hematopoietic Stem Cells, SSP Stem Cell Unit, Faculty of Medical Sciences, Kyushu University, Station for Collaborative Research1 4F, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Kasem Kulkeaw, Yuka Horio, Chiyo Mizuochi & Daisuke Sugiyama

  2. Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-8011, Japan

    Minetaro Ogawa

Authors
  1. Kasem Kulkeaw
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  2. Yuka Horio
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  3. Chiyo Mizuochi
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  4. Minetaro Ogawa
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  5. Daisuke Sugiyama
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Corresponding author

Correspondence to Daisuke Sugiyama.

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Author Contributions

Kasem Kulkeaw performed the experiments and analyzed data. Yuka Horio, Chiyo Mizuochi, and Minetaro Ogawa performed the experiments. Daisuke Sugiyama designed the experiments and wrote the manuscript.

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Kulkeaw, K., Horio, Y., Mizuochi, C. et al. Variation in Hematopoietic Potential of Induced Pluripotent Stem Cell Lines. Stem Cell Rev and Rep 6, 381–389 (2010). https://doi.org/10.1007/s12015-010-9150-5

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