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首页> 美国卫生研究院文献>Elsevier Sponsored Documents >Genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1) improves cell reprogramming efficiency and increases induced pluripotent stem cell proliferation and survival
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Genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1) improves cell reprogramming efficiency and increases induced pluripotent stem cell proliferation and survival

机译：哺乳动物不育20样激酶1（Mst1）的遗传消融可提高细胞重编程效率并提高诱导的多能干细胞增殖和存活率

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Adult fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) for use in various applications. However, there are challenges in iPSC generation including low reprogramming efficiency, yield, cell survival and viability. Since the Hippo signalling pathway is a key pathway involved in regulating cell proliferation and survival, we here test whether modification of the Hippo pathway will enhance the efficiency of iPSC generation and improve their survival.The Hippo pathway was modified by genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1), a major component of the pathway. Using adult skin fibroblasts isolated from Mst1 knockout mice (Mst1−/−) as a source of iPSC we found that genetic ablation of Mst1 leads to significantly increased reprogramming efficiency by 43.8%. Moreover, Mst1−/− iPSC displayed increase proliferation by 12% as well as an increase in cell viability by 20% when treated with a chemical hypoxic inducer. Mechanistically, we found higher activity of YAP, the main downstream effector of the Hippo pathway, in iPSC lacking Mst1.In conclusion, our data suggests that Mst1 can be targeted to improve the efficiency of adult somatic cell reprogramming as well as to enhance iPSC proliferation and survival.
机译：成人成纤维细胞可以重新编程为诱导性多能干细胞（iPSC），用于各种应用。但是，iPSC产生中存在挑战，包括低重编程效率，产量，细胞存活率和生存力。由于Hippo信号传导途径是调节细胞增殖和存活的关键途径，因此我们在此测试了Hippo途径的修饰是否会提高iPSC产生的效率并提高其存活率。 -20类似于激酶1（Mst1），是该途径的主要组成部分。使用从Mst1基因敲除小鼠（Mst1 -/-）分离的成年皮肤成纤维细胞作为iPSC的来源，我们发现Mst1的基因消融导致重编程效率显着提高了43.8％。此外，当用化学低氧诱导剂处理时，Mst1 -/- iPSC显示出增加的增殖12％以及细胞活力的增加20％。从机制上讲，我们发现缺乏Mst1的iPSC中HAP途径的主要下游效应物YAP的活性较高。总之，我们的数据表明Mst1可以靶向提高成人体细胞重编程的效率并增强iPSC的增殖。和生存。

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