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Orderly hematopoietic development of induced pluripotent stem cells via Flk-1+ hemoangiogenic progenitors

Authors

  • Akira Niwa,

    1. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    2. Clinical Application Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
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  • Katsutsugu Umeda,

    1. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • Hsi Chang,

    1. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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  • Megumu Saito,

    1. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    2. Clinical Application Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
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  • Keisuke Okita,

    1. Basic Biology Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
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  • Kazutoshi Takahashi,

    1. Basic Biology Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
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  • Masato Nakagawa,

    1. Basic Biology Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
    2. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
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  • Shinya Yamanaka,

    1. Basic Biology Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
    2. Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
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  • Tatsutoshi Nakahata,

    1. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    2. Clinical Application Department, Center for iPS cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan
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  • Toshio Heike

    Corresponding author
    1. Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    • Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
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  • The authors indicate no potential conflicts of interest.

Abstract

Induced pluripotent stem (iPS) cells, reprogrammed somatic cells with embryonic stem (ES) cell-like characteristics, are generated by the introduction of combinations of specific transcription factors. Little is known about the differentiation of iPS cells in vitro. Here we demonstrate that murine iPS cells produce various hematopoietic cell lineages when incubated on a layer of OP9 stromal cells. During this differentiation, iPS cells went through an intermediate stage consisting of progenitor cells that were positive for the early mesodermal marker Flk-1 and for the sequential expression of other genes that are associated with hematopoietic and endothelial development. Flk-1+ cells differentiated into primitive and definitive hematopoietic cells, as well as into endothelial cells. Furthermore, Flk-1+ populations contained common bilineage progenitors that could generate both hematopoietic and endothelial lineages from single cells. Our results demonstrate that iPS cell-derived cells, like ES cells, can follow a similar hematopoietic route to that seen in normal embryogenesis. This finding highlights the potential use of iPS cells in clinical areas such as regenerative medicine, disease investigation, and drug screening. J. Cell. Physiol. 221: 367–377, 2009. © 2009 Wiley-Liss, Inc.

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