Brief Report: L1 Cell Adhesion Molecule, a Novel Surface Molecule of Human Embryonic Stem cells, Is Essential for Self-Renewal and Pluripotency§

Authors

  • Yeon Sung Son,

    1. Therapeutic Antibody Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea
    2. School of Biological Sciences, Institute of Molecular Biology and Genetics, and Research Center for Functional Cellulomics, Seoul National University, Seoul, Republic of Korea
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  • Rho Hyun Seong,

    1. School of Biological Sciences, Institute of Molecular Biology and Genetics, and Research Center for Functional Cellulomics, Seoul National University, Seoul, Republic of Korea
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  • Chun Jeih Ryu,

    1. Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, Korea
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  • Yee Sook Cho,

    1. Development and Differentiation Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea
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  • Kwang-Hee Bae,

    1. Medical Proteomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea
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  • Sang J. Chung,

    1. BioNanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea
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  • Bonghee Lee,

    1. Center for Genomics and Proteomics, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Republic of Korea
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  • Jeong-Ki Min,

    Corresponding author
    1. Therapeutic Antibody Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea
    2. Department of Biomolecular Science, University of Science & Technology, Daejeon, Republic of Korea
    • Therapeutic Antibody Research Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea
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    • Telephone: 82-42-860-4137; Fax: 82-42-860-4149

  • Hyo Jeong Hong

    Corresponding author
    1. Department of Systems Immunology, Institute of Antibody Research, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea
    • Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701, Republic of Korea
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    • Telephone: 82-33-250-8381; Fax: 82-33-250-8380


  • Author contributions: Y.S.S.: conception and design, collection and assembly of data, and data analysis and interpretation; R.H.S.: administrative support and data analysis and interpretation; C.J.R.: conception and design; Y.S.C. and K.-H.B.: administrative support, data analysis, and financial support; S.J.C.: collection and assembly of data and financial support; B.-H.L.: administrative support and financial support; J.-K.M.: conception and design, collection and assembly of data, data analysis and interpretation, financial support, manuscript writing, and final approval of manuscript; H.J.H.: conception and design, data analysis and interpretation, financial support, and final approval of manuscript.

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

  • §

    First published online in STEM CELLSEXPRESS September 28, 2011.

Abstract

Despite the recent identification of surface markers of undifferentiated human embryonic stem cells (hESCs), the crucial cell-surface molecules that regulate the self-renewal capacity of hESCs remain largely undefined. Here, we generated monoclonal antibodies (MAbs) that specifically bind to undifferentiated hESCs but not to mouse embryonic stem cells. Among these antibodies, we selected a novel MAb, 4-63, and identified its target antigen as the L1 cell adhesion molecule (L1CAM) isoform 2. Notably, L1CAM expressed in hESCs lacked the neuron-specific YEGHH and RSLE peptides encoded by exons 2 and 27, respectively. L1CAM colocalized with hESC-specific cell-surface markers, and its expression was markedly downregulated on differentiation. Stable L1CAM depletion markedly decreased hESC proliferation, whereas L1CAM overexpression increased proliferation. In addition, the expression of octamer-binding transcription factor 4, Nanog, sex-determining region Y–box 2, and stage-specific embryonic antigen (SSEA)-3 was markedly downregulated, whereas lineage-specific markers and SSEA-1 were upregulated in L1CAM-depleted hESCs. Interestingly, the actions of L1CAM in regulating the proliferation and differentiation of hESCs were exerted predominantly through the fibroblast growth factor receptor 1 signaling pathway. Taken together, our results suggest that L1CAM is a novel cell-surface molecule that plays an important role in the maintenance of self-renewal and pluripotency in hESCs. Stem Cells 2011;29:2094–2099.

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