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Stem Cells. 2007 Dec;25(12):2996-3004. Epub 2007 Aug 23.

Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases Pim-1 and Pim-3.

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1
Institut National de la Santé et de la Recherche Médicale INSERM U846, 18 avenue Doyen Lépine, 69500 Bron, France.

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-ER(T2)), 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.

PMID:
17717068
DOI:
10.1634/stemcells.2007-0066
[Indexed for MEDLINE]
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