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

被引：60

作者：

Aksoy, Irene ^{[1
,2
,3
]}

Sakabedoyan, Caline ^{[1
,2
,3
]}

Bourillot, Pierre-Yves ^{[1
,2
,3
]}

Malashicheva, Anna B. ^{[1
,2
,3
]}

Mancip, Jimmy ^{[1
,2
,3
]}

Knoblauch, Kenneth ^{[1
,2
,3
]}

Afanassieff, Marielle ^{[1
,2
,3
]}

Savatier, Pierre ^{[1
,2
,3
]}

机构：

[1] INSERM, U846, F-69500 Bron, France

[2] Stem Cell & Brain Res Inst, F-69500 Bron, France

[3] Univ Lyon, Lyon, France

来源：

STEM CELLS | 2007年 / 25卷 / 12期

关键词：

embryonic stem cells; leukemia inhibitory factor; STAT3 transcription factor; pim kinases; cell cycle;

D O I：

10.1634/stemcells.2007-0066

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 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.

引用

页码：2996 / 3004

页数：9

共 34 条

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