Lack of ABCG2 Expression and Side Population Properties in Human Pluripotent Stem Cells§

Authors

  • Hui Zeng,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
    2. Departments of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, China
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  • Jung Woo Park,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Min Guo,

    1. Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, USA
    2. Departments of Geriatrics, Xiang-Ya Hospital, Central South University, Changsha, Hunan, China
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  • Ge Lin,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Leann Crandall,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Tiwanna Compton,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Xiaofang Wang,

    1. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Xue-Jun Li,

    1. University of Connecticut Stem Cell Institute, Farmington, Connecticut, USA
    2. Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut, USA
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  • Fang-Ping Chen,

    Corresponding author
    1. Departments of Hematology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, China
    • Department of Hematology, Xiang-Ya Hospital, Central South University, 87 Xiang-ya Road, Changsha, Hunan, 410008, China
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    • Telephone: 86-731-84327330; Fax: 86-731-84327332

  • Ren-He Xu

    Corresponding author
    1. University of Connecticut Stem Cell Institute, Farmington, Connecticut, USA
    2. Department of Genetics and Developmental Biology, University of Connecticut Stem Cell Institute, University of Connecticut Health Center, Farmington, Connecticut, USA
    • University of Connecticut Stem Cell Institute; Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut, 06030, USA
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    • Telephone: 860-679-3363; Fax: 860-679-8345


  • Author contributions: H.Z.: research conception and design, collection and/or assembly of data, data analysis, manuscript writing; J.W.P. and M.G.: collection and/or assembly of data, data analysis; G.L.: collection and/or assembly of data; L.C., T.C. and X.W.: provision of study material; X.-J.L.: research design; F.-P.C: research conception and design; R.-H.X.: research conception and design, data analysis, manuscript writing, final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS August 7, 2009.

Abstract

The multidrug transporter ABCG2 in cell membranes enables various stem cells and cancer cells to efflux chemicals, including the fluorescent dye Hoechst 33342. The Hoechst cells can be sorted out as a side population with stem cell properties. Abcg2 expression in mouse embryonic stem cells (ESCs) reduces accumulation of DNA-damaging metabolites in the cells, which helps prevent cell differentiation. Surprisingly, we found that human ESCs do not express ABCG2 and cannot efflux Hoechst. In contrast, trophoblasts and neural epithelial cells derived from human ESCs are ABCG2+ and Hoechst. Human ESCs ectopically expressing ABCG2 become Hoechst, more tolerant of toxicity of mitoxantrone, a substrate of ABCG2, and more capable of self-renewal in basic fibroblast growth factor (bFGF)-free condition than control cells. However, Hoechstlow cells sorted as a small subpopulation from human ESCs express lower levels of pluripotency markers than the Hoechsthigh cells. Similar results were observed with human induced pluripotent stem cells. Conversely, mouse ESCs are Abcg2+ and mouse trophoblasts, Abcg2. Thus, absence of ABCG2 is a novel feature of human pluripotent stem cells, which distinguishes them from many other stem cells including mouse ESCs, and may be a reason why they are sensitive to suboptimal culture conditions. STEM CELLS 2009;27:2435–2445

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