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

¹ Inserm, U846, 18 Avenue Doyen Lepine, 69500 Bron, France; Stem Cell and Brain Research Institute, 69500 Bron, France; Université de Lyon, Université, Lyon 1, 69003, Lyon, France

^* To whom correspondence should be addressed. E-mail: savatier{at}lyon.inserm.fr.

	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 analysed the regulation of pim-1 and pim-3 by the Leukemia Inhibitory Factor (LIF)/gp130/Signal Transducer and Activator of Transcription (STAT)-3 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 G-CSF:gp130 chimaeric receptor and a hormone-dependent STAT3-ER^T2, we showed that expression of pim-1 and pim-3 was up-regulated 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, knock-down of pim-1 and pim-3 increased the rate of spontaneous differentiation in a self-renewal assay. Knock-down of pim-1 and pim-3 were 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.