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

Stem Cells. 2007 Dec;25(12):2996-3004. doi: 10.1634/stemcells.2007-0066. Epub 2007 Aug 23.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Proliferation
  • Cells, Cultured
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / enzymology*
  • Mice
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-pim-1 / genetics
  • Proto-Oncogene Proteins c-pim-1 / physiology*

Substances

  • Proto-Oncogene Proteins
  • Pim3 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1