Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases pim-1 and pim-3
Self-renewal of murine embryonic stem cells is supported by the serine/threonine kinases pim-1 and pim-3
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DOI：
10.1634/stemcells.2007-0066
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发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Savatier, Pierre
中科院分区：
文献类型：
--
作者：
Aksoy, Irene;Sakabedoyan, Caline;Savatier, Pierre
PIM-1和PIM-3编码丝氨酸/苏氨酸激酶，其参与响应细胞因子刺激的细胞增殖和凋亡的调节。我们分析了白血病抑制因子（LIF）/gp 130/信号转导和转录激活因子-3（STAT 3）通路对pim-1和pim-3的调控以及Pim-1和Pim-3激酶在小鼠胚胎干细胞（ES细胞）自我更新中的作用。利用表达粒细胞集落刺激因子：gp 130嵌合受体和雌激素依赖性信号转导和转录激活因子-3雌激素受体（STAT 3-ERT 2）的ES细胞，我们发现pim-1和3的表达上调LIF/gp 130依赖性信号传导和STAT 3转录因子。过表达pim-1和pim-3的ES细胞具有更大的自我更新能力，并显示出更大的抵抗基于克隆测定的LIF饥饿。相反，在自我更新试验中，pim-1和pim-3的敲低增加了自发分化的速率。敲低pim-1和pim-3也不利于未分化ES细胞集落的生长，并增加凋亡率。这些发现提供了一个新的作用Pim-1和Pim-3激酶在控制自我更新的ES细胞。
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.