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首页> 外文期刊>Cell cycle >Molecular basis for an attenuated cytoplasmic dsRNA response in human embryonic stem cells.
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Molecular basis for an attenuated cytoplasmic dsRNA response in human embryonic stem cells.

机译：人类胚胎干细胞中胞质dsRNA减毒反应的分子基础。

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The introduction of double stranded RNA (dsRNA) into the cytoplasm of mammalian cells usually leads to a potent antiviral response resulting in the rapid induction of interferon beta (IFNbeta). This response can be mediated by a number of dsRNA sensors, including TLR3, MDA5, RIG-I and PKR. We show here that pluripotent human cells (human embryonic stem (hES) cells and induced pluripotent (iPS) cells) do not induce interferon in response to cytoplasmic dsRNA, and we have used a variety of approaches to learn the underlying basis for this phenomenon. Two major cytoplasmic dsRNA sensors, TLR3 and MDA5, are not expressed in hES cells and iPS cells. PKR is expressed in hES cells, but is not activated by transfected dsRNA. In addition, RIG-I is expressed, but fails to respond to dsRNA because its signaling adapter, MITA/STING, is not expressed. Finally, the interferon-inducible RNAse L and oligoadenylate synthetase enzymes are also expressed at very low levels. Upon differentiation of hES cells into trophoblasts, cells acquire the ability to respond to dsRNA and this correlates with a significant induction of expression of TLR3 and its adaptor protein TICAM-1/TRIF. Taken together, our results reveal that the lack of an interferon response may be a general characteristic of pluripotency and that this results from the systematic downregulation of a number of genes involved in cytoplasmic dsRNA signaling.
机译：将双链RNA（dsRNA）引入哺乳动物细胞的细胞质通常会导致有效的抗病毒反应，从而导致干扰素β（IFNbeta）的快速诱导。此反应可以通过许多dsRNA传感器介导，包括TLR3，MDA5，RIG-1和PKR。我们在这里表明，多能人类细胞（人类胚胎干细胞（hES）和诱导多能性（iPS）细胞）不会诱导对细胞质dsRNA的干扰素，并且我们已经使用多种方法来了解这种现象的潜在基础。在hES细胞和iPS细胞中未表达两种主要的胞质dsRNA传感器TLR3和MDA5。 PKR在hES细胞中表达，但未被转染的dsRNA激活。此外，RIG-I被表达，但由于未表达其信号转导接头MITA / STING而无法响应dsRNA。最后，干扰素诱导的RNA酶L和寡腺苷酸合成酶也以非常低的水平表达。在将hES细胞分化为滋养细胞后，细胞获得了对dsRNA的反应能力，这与TLR3及其衔接蛋白TICAM-1 / TRIF表达的显着诱导相关。两者合计，我们的结果表明，干扰素反应的缺乏可能是多能性的一般特征，并且这是由于系统地下调了参与细胞质dsRNA信号传导的许多基因而导致的。

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