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

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.

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