Self-Renewal of Murine Embryonic Stem Cells Is Supported by the Serine/Threonine Kinases Pim-1 and Pim-3

Authors

  • Irène Aksoy,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Caline Sakabedoyan,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Pierre-Yves Bourillot,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Anna B. Malashicheva,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Jimmy Mancip,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Kenneth Knoblauch,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Marielle Afanassieff,

    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
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  • Pierre Savatier Ph.D.

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale, Bron, France
    2. Stem Cell and Brain Research Institute, Bron, France
    3. Université de Lyon, Lyon, France
    • INSERM U846, 18 avenue Doyen Lépine, 69500 Bron, France. Telephone: 33-472-91-34-42; Fax: 33-472-91-34-61
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Abstract

pim-1 and pim-3 encode serine/threonine kinases involved in the regulation of cell proliferation and apoptosis in response to cytokine stimulation. We analyzed the regulation of pim-1 and pim-3 by the leukemia inhibitory factor (LIF)/gp130/signal transducer and activator of transcription-3 (STAT3) pathway and the role of Pim-1 and Pim-3 kinases in mouse embryonic stem (ES) cell self-renewal. Making use of ES cells expressing a granulocyte colony-stimulating factor:gp130 chimeric receptor and a hormone-dependent signal transducer and activator of transcription-3 estrogen receptor (STAT3-ERT2), we showed that expression of pim-1 and pim-3 was upregulated by LIF/gp130-dependent signaling and the STAT3 transcription factor. ES cells overexpressing pim-1 and pim-3 had a greater capacity to self-renew and displayed a greater resistance to LIF starvation based on a clonal assay. In contrast, knockdown of pim-1 and pim-3 increased the rate of spontaneous differentiation in a self-renewal assay. Knockdown of pim-1 and pim-3 was also detrimental to the growth of undifferentiated ES cell colonies and increased the rate of apoptosis. These findings provide a novel role of Pim-1 and Pim-3 kinases in the control of self-renewal of ES cells.

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

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