Open AccessSelf‐Renewal of Murine Embryonic Stem Cells Is Supported by the Serine/Threonine Kinases Pim‐1 and Pim‐3
Author(s) -
Aksoy Irène,
Sakabedoyan Caline,
Bourillot PierreYves,
Malashicheva Anna B.,
Mancip Jimmy,
Knoblauch Kenneth,
Afanassieff Marielle,
Savatier Pierre
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0066
Subject(s) - biology , embryonic stem cell , serine , threonine , kinase , microbiology and biotechnology , stem cell , protein serine threonine kinases , phosphorylation , biochemistry , protein kinase a , gene
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.