Multipotent adult germline stem cells and embryonic stem cells functional proteomics revealed an important role of eukaryotic initiation factor 5A (Eif5a) in stem cell differentiation.
Multipotent adult germline stem cells and embryonic stem cells functional proteomics revealed an important role of eukaryotic initiation factor 5A (Eif5a) in stem cell differentiation.
复制标题
DOI：
10.1021/pr1012015
复制
发表时间：
2011-03
影响因子：
4.4
通讯作者：
H. Dihazi;G. H. Dihazi;O. Jahn;S. Meyer;J. Nolte;A. R. Asif;G. Mueller;W. Engel
中科院分区：
文献类型：
--
作者：
H. Dihazi;G. H. Dihazi;O. Jahn;S. Meyer;J. Nolte;A. R. Asif;G. Mueller;W. Engel
多能成体生殖系干细胞(MaGSCs)是一种多能细胞，可分化为三个初级生殖层的体细胞。为了突出与干细胞分化相关的蛋白质谱变化，将维甲酸(RA)处理的小鼠干细胞(maGSCs和ESCs)与未处理的干细胞进行了比较。建立2-DE和DGE参考图谱，并进一步处理差异表达蛋白质进行鉴定。在这两种干细胞类型中，RA诱导的分化导致36个蛋白质的改变，其中18个蛋白质表达下调，可能是潜在的多能性相关蛋白，而另外18个蛋白质表达上调。这些可能与干细胞分化有关。令人惊讶的是，真核细胞起始因子5A(Eif5a)是一种对细胞增殖和分化至关重要的蛋白质，在RA处理下显著下调。对Eif5a的时间依赖性研究表明，干细胞的RA处理导致Eif5a在前48小时显着上调，随后逐渐下调。这一作用可被激素化抑制剂环吡酮胺(CPX)阻断。质谱学证实，Eif5a激活的改变对体外培养的ESCs和maGSCs具有抗增殖作用，但不影响细胞的多能性。我们的数据强调了Eif5a及其激活对干细胞分化和增殖的重要作用。
Multipotent adult germline stem cells (maGSCs) are pluripotent cells that can be differentiated into somatic cells of the three primary germ layers. To highlight the protein profile changes associated with stem cell differentiation, retinoic acid (RA) treated mouse stem cells (maGSCs and ESCs) were compared to nontreated stem cells. 2-DE and DIGE reference maps were created, and differentially expressed proteins were further processed for identification. In both stem cell types, the RA induced differentiation resulted in an alteration of 36 proteins of which 18 were down-regulated and might be potential pluripotency associated proteins, whereas the other 18 proteins were up-regulated. These might be correlated to stem cell differentiation. Surprisingly, eukaryotic initiation factor 5A (Eif5a), a protein which is essential for cell proliferation and differentiation, was significantly down-regulated under RA treatment. A time-dependent investigation of Eif5a showed that the RA treatment of stem cells resulted in a significant up-regulation of the Eif5a in the first 48 h followed by a progressive down-regulation thereafter. This effect could be blocked by the hypusination inhibitor ciclopirox olamine (CPX). The alteration of Eif5a hypusination, as confirmed by mass spectrometry, exerts an antiproliferative effect on ESCs and maGSCs in vitro, but does not affect the cell pluripotency. Our data highlights the important role of Eif5a and its hypusination for stem cell differentiation and proliferation.