Embryoid body formation of human amniotic fluid stem cells depends on mTOR.

Embryoid body formation of human amniotic fluid stem cells depends on mTOR.
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DOI:
10.1038/onc.2009.405
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发表时间:
2010-02-18
期刊:
影响因子:
8
通讯作者:
Hengstschläger M
Hengstschläger M
中科院分区:
医学1区
文献类型:
--
作者:
Valli A;Rosner M;Fuchs C;Siegel N;Bishop CE;Dolznig H;Mädel U;Feichtinger W;Atala A;Hengstschläger M

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人羊水干细胞(hAFSC)具有高增殖能力和高分化潜能,不会引起与人胚胎干细胞相关的伦理问题。被称为胚状体(EBs)的三维聚集体的形成是多能胚胎干细胞分化的主要步骤。使用c-Kit阳性hAFSC系,我们在这里显示这些干细胞具有形成EB的潜力。哺乳动物雷帕霉素靶蛋白(mTOR)作为mTORC 1和mTORC 2两种激酶复合物的一部分,是一条重要的信号通路的关键组分,参与调节细胞增殖、生长、肿瘤的发生和分化。通过抑制剂雷帕霉素或通过特异性小干扰RNA方法阻断细胞内mTOR活性揭示了hAFSC EB形成依赖于mTORC 1和mTORC 2。这些发现表明hAFSC是一种新的和强大的生物系统,可以概括体内发育的三维和组织水平背景,并确定mTOR通路对该过程至关重要。
Human amniotic fluid stem cells (hAFSCs) harbor high proliferative capacity and high differentiation potential and do not raise the ethical concerns associated with human embryonic stem cells. The formation of three-dimensional aggregates known as embryoid bodies (EBs) is the principal step in the differentiation of pluripotent embryonic stem cells. Using c-Kit-positive hAFSC lines, we show here that these stem cells harbor the potential to form EBs. As part of the two kinase complexes, mTORC1 and mTORC2, mammalian target of rapamycin (mTOR) is the key component of an important signaling pathway, which is involved in the regulation of cell proliferation, growth, tumor development and differentiation. Blocking intracellular mTOR activity through the inhibitor rapamycin or through specific small interfering RNA approaches revealed hAFSC EB formation to depend on mTORC1 and mTORC2. These findings demonstrate hAFSCs to be a new and powerful biological system to recapitulate the three-dimensional and tissue level contexts of in vivo development and identify the mTOR pathway to be essential for this process.
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